Document:

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                                                                   EXHIBIT 10.16

                          FOURTH AMENDMENT TO CERTAIN
                              OPERATIVE AGREEMENTS

     THIS FOURTH AMENDMENT TO CERTAIN OPERATIVE AGREEMENTS dated as of December
31, 2000 (this "Amendment") is by and among AOR SYNTHETIC REAL ESTATE, INC., a
Delaware corporation (the "Lessee" or the "Construction Agent" or a "Tranche A
Guarantor"); US ONCOLOGY, INC. (formerly American Oncology Resources, Inc.) a
Delaware corporation (the "Guarantor" or a "Tranche A Guarantor"); the various
entities which are parties hereto as guarantors of the Tranche A Loans (subject
to the definition of Tranche A Guarantors in Appendix A of the Participation
Agreement, as defined below, individually a "Tranche A Guarantor" and
collectively, the "Tranche A Guarantors"); FIRST SECURITY BANK, NATIONAL
ASSOCIATION, a national banking association, not individually, but solely as the
Owner Trustee under the AOR Trust 1997-1 (the "Owner Trustee", the "Borrower" or
the "Lessor"); the various banks and other lending institutions which are
parties hereto as lenders (subject to the definition of Lenders in Appendix A of
the Participation Agreement, individually, a "Lender" and collectively, the
"Lenders"); the various banks and other lending institutions which are parties
hereto as holders of certificates issued with respect to the AOR Trust 1997-1
(subject to the definition of Holders in Appendix A of the Participation
Agreement, individually, a "Holder" and collectively, the "Holders"); and FIRST
UNION NATIONAL BANK, a national banking association ("FUNB"), as the agent for
the Lenders and respecting the Security Documents, as the agent for the Lenders
and the Holders, to the extent of their interests (in such capacity, the
"Agent").

                              W I T N E S S E T H:

     WHEREAS, each of the parties hereto has agreed to amend the pricing matrix
set forth in the definition of Applicable Margin; and

     WHEREAS, the parties to this Amendment wish to amend certain agreements,
instruments and other documents to which they are a party (or to which certain
of them are a party) in connection with a lease financing arrangement provided
in favor of Lessee by the other parties to this Amendment with regard to the
Properties.

                               A G R E E M E N T

     NOW, THEREFORE, for good and valuable consideration, the receipt and
sufficiency of which are hereby acknowledged, the parties to this Amendment
agree as follows:

     1.  Definitions.  Capitalized terms used herein but not otherwise defined
herein shall have the meaning set forth therefor in Appendix A to the
Participation Agreement.  The rules of usage set forth in Appendix A to the
Participation Agreement shall apply herein.  In the case of any conflict between
the provisions of this Amendment and the provisions of the Operative Agreements,
the provisions of this Amendment shall control construction of the terms.
<PAGE>

     2.  Incorporation of Amended Incorporated Covenants and Terms.  Each of the
of the  parties to this Amendment hereby acknowledges the amendments to the
Incorporated Covenants and the Additional Incorporated Terms as set forth in the
Second Amendment to the Lessee Credit Agreement, which amendment is dated as of
December 31, 2000 among US Oncology, Inc., the banks and other financial
institutions party to the Lessee Credit Agreement and First Union National Bank
(the "Second Amendment to the Lessee Credit Agreement"), substantially in the
form of Exhibit A attached hereto, and each party hereto agrees that no consent
of any party to any of the Operative Agreements is required in connection
therewith.

     3.   Appendix A to the Participation Agreement.  Appendix A to the
Participation Agreement is amended as follows:

          (a) by adding the following definition in appropriate alphabetical
     order:

          ""Fourth Amendment" shall mean the Fourth Amendment to Certain
          Operative Agreements dated as of December 31, 2000 by and among the
          parties to the Participation Agreement as of such date.";

          (b)  The definition of "Annualized EBITDA" is hereby amended and
     restated in its entirety as follows:

          ""Annualized EBITDA" shall mean, with respect to AOR and its
          Subsidiaries, on a consolidated basis, as of the last day of any
          fiscal quarter, EBITDA for the period of four consecutive fiscal
          quarters then ending.";

          (c) The definition for "Applicable Margin" is amended by deleting the
     matrix contained therein in its entirety and replacing it with the
     following matrix:

<TABLE>
<CAPTION>
              Ratio of Consolidated                Applicable Margin for    Applicable Margin for    Applicable Margins for
                    Debt to                              Eurodollar               Eurodollar               Eurodollar
               Annualized EBITDA                      Tranche A Loans          Tranche B Loans           Holder Advances
               -----------------                   ----------------------   ----------------------   -----------------------

<S>                                                <C>                      <C>                      <C>
Greater than 3.00 to 1.00                                  1.825%                   2.200%                    2.575%

Greater than 2.50 to 1.00 but less than or                 1.725%                   2.100%                    2.475%
 equal to 3.00 to 1.00

Greater than 2.00 to 1.00 but less than or                 1.600%                   1.975%                    2.350%
 equal to 2.50 to 1.00

Greater than 1.50 to 1.00 but less than or                 1.500%                   1.875%                    2.250%
 equal to 2.00 to 1.00

Greater than 1.00 to 1.00 but less than or                 1.375%                   1.750%                    2.125%
 equal to 1.50 to 1.00

Less than or equal to 1.00 to 1.00                         1.275%                   1.650%                    2.025%
</TABLE>

                                       2
<PAGE>

          (d)  The definition of "EBITDA" is hereby amended and restated in its
     entirety as follows:

          ""EBITDA" shall mean, for any period, an amount equal to, without
          duplication, the sum of (a) net income (determined in accordance with
          GAAP) earned in such period, plus (b) to the extent net income has
          been reduced thereby, the sum of (i) depreciation and amortization
          expense, plus (ii) Interest Expense, plus (iii) federal and state
          income taxes, plus (c) to the extent net income has been reduced
          thereby in the fiscal quarters ending December 31, 2000, March 31,
          2001, June 30, 2001 and September 30, 2001, (A) nonrecurring non-cash
          charges arising from the write-off of corporate non-core and under
          performing assets and the write-down or write-off of certain other
          assets (in an aggregate amount not to exceed $200,000,000) and (B)
          cash expenses arising from the costs associated with employee and
          corporate reorganization, including without limitation the closing of
          offices and the elimination, relocation and consolidation of certain
          employment positions, and other related costs (in an aggregate amount
          not to exceed $15,000,000)."

     4.   Effective Date.  Provided each of the conditions set forth in Section
4(a)-(e)(d) hereof has been satisfied or waived in accordance with the terms of
this Section 4, each of the provisions in this Amendment shall be effective from
and after December 31, 2000, except Section 3(b) of this Amendment which shall
be effective from and after March ___, 2001.  This Amendment shall be effective
in accordance with the terms and conditions hereof provided each of the
following has been satisfied or waived (provided, that any such waiver shall
require subsequent satisfaction (unless expressly stated to be a permanent
waiver) of any such condition so waived), each in the Agent's reasonable
discretion:

          (a) The Second Amendment to the Lessee Credit Agreement shall be in
     full force and effect prior to or simultaneous with the effectiveness of
     this Amendment;

          (b) Each of the conditions to effectiveness set forth in the Second
     Amendment to the Lessee Credit Agreement, including without limitation the
     payment of the fee set forth in Section 4.5 thereof to each Lender and
     Holder and the conditions set forth in Section 4.9 thereof, shall have been
     satisfied;

          (c) All entities subject to the requirements of Section 5.8 of the
     Participation Agreement prior to the date first set forth above shall have
     satisfied in full all such requirements; and

          (d) Each of the parties hereto shall have delivered to the Agent their
     respective signature pages, executed by an authorized officer of such
     party.

     5.   Credit Party Representations and Warranties.  As of March __, 2001,
each and every representation and warranty of each Credit Party contained in the
Operative Agreements (except for any such representations and warranties which
relate solely to an earlier time) is true

                                       3
<PAGE>

and correct and no Default or Event of Default has occurred and is continuing
under any Operative Agreement.

     6.   Enforceability.  Each Operative Agreement, including without
limitation this Amendment, to which any Credit Party is a party is in full force
and effect with respect to it.

     7.   Counterparts.  This Amendment may be executed in any number of
counterparts, each of which when executed and delivered shall be deemed to be an
original and it shall not be necessary in making proof of this Amendment to
produce or account for more than one such counterpart provided, that to the
extent this Amendment constitutes chattel paper (as such term is defined in the
Uniform Commercial Code), no Lien on this Amendment may be created or perfected
through the transfer or possession of any counterpart hereof other than the
counterpart bearing the receipt therefor executed by the Agent on the signature
page hereof, which counterpart shall constitute the only "original" hereof for
purposes of the Uniform Commercial Code.

     8.   Continued Effectiveness of Operative Agreements.  Except as
modified hereby, all of the terms and conditions of the Operative Agreements are
hereby ratified and affirmed and  shall remain in full force and effect. The
parties acknowledge that this Amendment complies with Section 12.4 of the
Participation Agreement and any noncompliance is deemed waived, subject to the
unanimous vote provisions contained therein.

     9.   Direction to Agent and Lessor.  Each of the Lenders and Holders
hereby instructs the Agent and the Lessor to enter into this Amendment.

     10.  Severability.  Any provision of this Amendment that is prohibited or
unenforceable in any jurisdiction shall, as to such jurisdiction, be ineffective
to the extent of such prohibition or unenforceability without invalidating the
remaining provisions hereof, and any such prohibition or unenforceability in any
jurisdiction shall not invalidate or render unenforceable such provision in any
other jurisdiction.

     11.  Further Assurance and Headings.  The provisions of the Participation
Agreement relating to Further Assurances and Headings are hereby incorporated by
reference herein, mutatis mutandis.

     12.  Governing Law.  This Amendment shall be governed by, and construed
in accordance with, the laws of the State of North Carolina except as to the
Trust Agreement which shall be governed by, and construed in accordance with,
the laws of the State of Utah.

     13.  JURISDICTION, VENUE AND ARBITRATION.  THE PROVISIONS OF THE
PARTICIPATION AGREEMENT RELATING TO SUBMISSION TO JURISDICTION, VENUE AND
ARBITRATION ARE HEREBY INCORPORATED BY REFERENCE HEREIN, MUTATIS MUTANDIS.

                                       4
<PAGE>

     14.  Fees and Expenses.  The Lessee agrees to pay all reasonable costs
and expenses of the Agent in connection with the preparation, execution and
delivery of this Amendment, including without limitation the reasonable fees of
Moore & Van Allen, PLLC.

Any and all Operative Agreements, notices, requests, certificates and other
instruments executed and delivered prior to or after the execution and delivery
of this Amendment may refer to  "American Oncology Resources, Inc.", "AOR" or
may identify such entity in any other respect, but nevertheless all such
references shall be deemed to refer to US Oncology, Inc., a Delaware corporation
(formerly American Oncology Resources, Inc.) and its successors and permitted
assigns, unless the context shall otherwise require.

        [The remainder of this page has been intentionally left blank.]

                                       5
<PAGE>

     IN WITNESS WHEREOF, each of the parties hereto has caused this Amendment to
be duly executed and delivered as of the date first above written.

                    AOR SYNTHETIC REAL ESTATE, INC., as the Construction Agent,
                      as the Lessee and as a Tranche A Guarantor

                    US ONCOLOGY, INC. (formerly known as AMERICAN ONCOLOGY
                      RESOURCES, INC.), as the Guarantor and as a Tranche A
                      Guarantor

                    AOR REAL ESTATE, INC., as a Tranche A Guarantor
                    US ONCOLOGY CORPORATE, INC. (formerly known as
                      AOR, INC.), as a Tranche A Guarantor
                    RMCC CANCER CENTER INC., as a Tranche A Guarantor
                    AOR MANAGEMENT COMPANY OF OREGON, INC.,
                      as a Tranche A Guarantor
                    AOR MANAGEMENT COMPANY OF INDIANA, INC.,
                      as a Tranche A Guarantor
                    AOR MANAGEMENT COMPANY OF MISSOURI, INC.,
                      as a Tranche A Guarantor
                    AOR MANAGEMENT COMPANY OF ARIZONA, INC.,
                      as a Tranche A Guarantor
                    AOR MANAGEMENT COMPANY OF SOUTH CAROLINA, INC.,
                      as a Tranche A Guarantor
                    AOR MANAGEMENT COMPANY OF OKLAHOMA, INC.,
                      as a Tranche A Guarantor
                    AOR MANAGEMENT COMPANY OF PENNSYLVANIA, INC.,
                      as a Tranche A Guarantor
                    AOR MANAGEMENT COMPANY OF VIRGINIA, INC.,
                      as a Tranche A Guarantor
                    AOR MANAGEMENT COMPANY OF NORTH CAROLINA, INC.,
                      as a Tranche A Guarantor
                    AOR MANAGEMENT COMPANY OF NEW YORK, INC.,
                      as a Tranche A Guarantor
                    AOR MANAGEMENT COMPANY OF FLORIDA, INC.,
                      as a Tranche A Guarantor
                    AOR MANAGEMENT COMPANY OF NEVADA, INC.,
                      as a Tranche A Guarantor
                    AOR HOLDING COMPANY OF INDIANA, INC.,
                      as a Tranche A Guarantor
                    AOR MANAGEMENT COMPANY OF TEXAS, INC.,
                      as a Tranche A Guarantor

                          [SIGNATURE PAGES CONTINUED]
<PAGE>

                    AOR MANAGEMENT COMPANY OF CENTRAL FLORIDA, INC.,
                      as a Tranche A Guarantor
                    AOR MANAGEMENT COMPANY OF OHIO, INC.,
                       as a Tranche A Guarantor
                    AOR MANAGEMENT COMPANY OF KANSAS, INC.,
                      as a Tranche A Guarantor
                    AORT HOLDING COMPANY, INC., as a Tranche A Guarantor
                    AORIP, Inc., as a Tranche A Guarantor
                    AOR MANAGEMENT COMPANY OF ALABAMA, INC., as a Tranche A
                      Guarantor
                    GREENVILLE RADIATION CARE, INC., as a Tranche A Guarantor
                    PHYSICIAN RELIANCE NETWORK, INC., as a Tranche A Guarantor
                    TOPS PHARMACY SERVICES, INC., as a Tranche A Guarantor
                    US ONCOLOGY RESEARCH, INC. (formerly known as PRN RESEARCH,
                      INC.), as a Tranche A Guarantor
                    NORTHWEST CANCER CENTER, INC. (formerly Washington Cancer
                      Centers, P.C.), as a Tranche A Guarantor
                    PRN PHYSICIAN RELIANCE, LLC, as a Tranche A Guarantor
                    PHYSICIAN RELIANCE HOLDINGS, LLC (formerly known as
                    PHYSICIAN RELIANCE INVESTMENTS, LLC), as a Tranche A
                      Guarantor

                    By:___________________________
                    Name:_________________________
                    Title:________________________
                          of each of the other foregoing entities

                    AOR of Texas Management Limited Partnership,
                    a Texas limited partnership, as a Tranche A Guarantor

                    by:  AOR MANAGEMENT COMPANY OF TEXAS, INC.,
                    a Delaware corporation, as general partner

                    By:___________________________
                    Name:_________________________
                    Title:________________________

                          [SIGNATURE PAGES CONTINUED]
<PAGE>

                    AOR OF INDIANA MANAGEMENT PARTNERSHIP,
                    an Indiana general partnership, as a Tranche A Guarantor

                    By:  AOR MANAGEMENT COMPANY OF INDIANA, INC., a Delaware
                         corporation, as general partner

                    By:___________________________
                    Name:_________________________
                    Title:________________________

                    By:  AOR HOLDING COMPANY OF INDIANA, INC., a Delaware
                         corporation, as general partner

                    By:___________________________
                    Name:_________________________
                    Title:________________________

                    PHYSICIAN RELIANCE, L.P.,
                    A Texas limited partnership, as a Tranche A Guarantor

                    By:  PRN PHYSICIAN RELIANCE, LLC, a Texas limited liability
                         company, as general partner

                    By:  PHYSICIAN RELIANCE HOLDINGS, LLC (formerly known as
                         PHYSICIAN RELIANCE INVESTMENTS, LLC), a Texas limited
                         liability company, as limited partner

                    By:___________________________
                    Name:_________________________
                    Title:________________________

                          [Signature pages continued]
<PAGE>

                    FIRST SECURITY BANK, NATIONAL ASSOCIATION,
                    not individually, but solely as Owner Trustee under the AOR
                    Trust 1997-1

                    By:___________________________
                    Name:_________________________
                    Title:________________________

                          [Signature pages continued]
<PAGE>

                    FIRST UNION NATIONAL BANK, as a Lender
                    and as a Holder

                    By:___________________________
                    Name:_________________________
                    Title:________________________

                          [SIGNATURE PAGES CONTINUED]

<PAGE>

                    BANK ONE, NA (formerly The First National Bank of Chicago),
                    as a Lender and as a Holder

                    By:___________________________
                    Name:_________________________
                    Title:________________________

                          [SIGNATURE PAGES CONTINUED]

<PAGE>

                    COOPERATIEVE CENTRALE
                    RAIFFEISEN-BOERENLEENBANK B.A.
                    "Rabobank Nederland", NEW YORK BRANCH,
                    as a Lender and as a Holder

                    By:___________________________
                    Name:_________________________
                    Title:________________________

                    By:___________________________
                    Name:_________________________
                    Title:________________________

                          [SIGNATURE PAGES CONTINUED]

<PAGE>

                    BANKERS TRUST COMPANY,
                    as a Lender

                    By:___________________________
                    Name:_________________________
                    Title:________________________

                          [SIGNATURE PAGES CONTINUED]

<PAGE>

                    WELLS FARGO BANK (TEXAS), NATIONAL ASSOCIATION,
                    as a Lender

                    By:___________________________
                    Name:_________________________
                    Title:________________________

                          [SIGNATURE PAGES CONTINUED]

<PAGE>

                    THE CHASE MANHATTAN BANK,
                    as a Lender and as a Holder

                    By:___________________________
                    Name:_________________________
                    Title:________________________

                          [SIGNATURE PAGES CONTINUED]

<PAGE>

                    BANK OF AMERICA, N.A. (formerly NationsBank, N.A.),
                    as a Lender

                    By:___________________________
                    Name:_________________________
                    Title:________________________

                          [SIGNATURE PAGES CONTINUED]

<PAGE>

                    CREDIT LYONNAIS NEW YORK BRANCH,
                    as a Lender

                    By:___________________________
                    Name:_________________________
                    Title:________________________

                          [SIGNATURE PAGES CONTINUED]

<PAGE>

                    U.S. BANK NATIONAL ASSOCIATION,
                    as a Lender

                    By:___________________________
                    Name:_________________________
                    Title:________________________

                          [SIGNATURE PAGES CONTINUED]

<PAGE>

     Receipt of the original counterpart of the foregoing Amendment is hereby
acknowledged on this ____ day of ______________, 1999./1/

                                   FIRST UNION NATIONAL BANK, as Agent

                                   By:___________________________
                                   Name:_________________________
                                   Title:________________________

                             [SIGNATURE PAGES END]

----------------
/1/ This acknowledgment is executed in the orginal coutnerpart only.
<PAGE>

                                   EXHIBIT A

                 [SECOND AMENDMENT TO LESSEE CREDIT AGREEMENT]<PAGE>

                                                                   EXHIBIT 10.17

                     AMENDMENT TO NOTE PURCHASE AGREEMENTS

     THIS AMENDMENT TO NOTE PURCHASE AGREEMENTS (this "Amendment") dated as of
March 23, 2001 is made among US ONCOLOGY, INC., a Delaware corporation (the
"Company"), and the undersigned holders (the "Holders") of the Company's 8.42%
Senior Secured Notes due November 2006 (the "Notes").

                                    RECITALS

     A.  The Company and the Holders have each entered into a Note Purchase
Agreement dated November 24, 1999 (each a "Note Purchase Agreement" and
collectively, the "Note Purchase Agreements") with respect to the purchase and
sale of $100,000,000 of Notes. Capitalized terms not otherwise defined herein
shall have the meanings set forth in the Note Purchase Agreements.

     B.  The Company has requested certain amendments to the Note Purchase
Agreements so that the Company will be permitted to add back to Consolidated
Income Available for Fixed Charges and Consolidated Net Worth the effect of
certain charges associated with the write-off of certain assets, the closing of
certain offices and the elimination of certain employment positions, and the
Holders have agreed to make such amendments on the terms and conditions set
forth herein.

     NOW, THEREFORE, for good and valuable consideration, the receipt and
sufficiency of which are hereby acknowledged, the Company and the Holders hereby
agree as follows:

                                  ARTICLE 1.

                                  AMENDMENTS

     1.1  AMENDMENT TO SCHEDULE B - DEFINED TERMS. SCHEDULE B of each of the
Note Purchase Agreements is hereby amended as follows:

          (a)  The definition of "Consolidated Fixed Charges" is hereby amended
     and restated in its entirety as follows:

               "CONSOLIDATED FIXED CHARGES" means for the immediate past four
     fiscal quarters the sum of consolidated interest expense (which includes
     capitalized interest and the interest component of Capitalized Leases) plus
     actual rent payments under operating leases and including in all instances
     interest expense and rent pursuant to the ELLF and any other tax retention
     operating lease or synthetic lease.

          (b)  The definition of "Consolidated Income Available for Fixed
     Charges" is hereby amended and restated in its entirety as follows:

               "CONSOLIDATED INCOME AVAILABLE FOR FIXED CHARGES" means with
     respect to any period, Consolidated Net Income for such period plus (to the
     extent deducted in calculating Consolidated Net Income):
<PAGE>

               (a) all provisions for income taxes;

               (b) Consolidated Fixed Charges for such period; and

               (c) if such period includes any of the fiscal quarters ending
     December 31, 2000, March 31, 2001, June 30, 2001 and September 30, 2001,
     the amount by which Consolidated Net Income for such fiscal quarters has
     been reduced on account of (i) nonrecurring non-cash charges arising from
     the write-off of corporate non-core and under performing assets and the
     write-down or write-off of certain other assets (in an aggregate amount not
     to exceed $200,000,000) and (ii) cash expenses arising from the costs
     associated with employee and corporate reorganization, including without
     limitation the closing of offices and the elimination, relocation and
     consolidation of certain employment positions, and other related costs (in
     an aggregate amount not to exceed $15,000,000).

     (c)  The definition of "Consolidated Net Worth" is hereby amended and
restated in its entirety as follows:

               "CONSOLIDATED NET WORTH" means (i) the stockholders' equity of
     the Company determined in accordance with GAAP plus (ii) the amount by
     which Consolidated Net Income for the fiscal quarters ending December 31,
     2000, March 31, 2001, June 30, 2001 and September 30, 2001 has been reduced
     on account of (A) nonrecurring non-cash charges arising from the write-off
     of corporate non-core and under performing assets and the write-down or
     write-off of certain other assets (in an aggregate amount not to exceed
     $200,000,000) and (B) cash expenses arising from the costs associated with
     employee and corporate reorganization, including without limitation the
     closing of offices and the elimination, relocation and consolidation of
     certain employment positions, and other related costs (in an aggregate
     amount not to exceed $15,000,000).

     (d)  The definition of "Consolidated Operating Cash Flow" is hereby amended
and restated in its entirety as follows:

               "CONSOLIDATED OPERATING CASH FLOW" means Consolidated Net Income
     for the immediately preceding four fiscal quarters plus (to the extent
     deducted in calculating Consolidated Net Income):

               (a) provisions for federal, state and local income taxes;

               (b) interest expense and lease payments made by the Company and
     its Subsidiaries pursuant to the ELLF and any other tax retention operating
     lease or synthetic lease that is treated as a Capitalized Lease;

               (c) nonrecurring items to the extent deducted in calculating
     Consolidated Net Income; and

               (d) depreciation and amortization;

                                       2
<PAGE>

                   all determined in accordance with GAAP.

          (e)  The definition of "Indebtedness" is hereby amended and
restated in its entirety as follows:

               "INDEBTEDNESS" with respect to any Person means, at any time,
     without duplication,

               (a)  its liabilities for borrowed money and its redemption
     obligations in respect of mandatorily redeemable Preferred Stock;

               (b)  liabilities for the deferred purchase price of property
     acquired by such Person (excluding accounts payable arising in the ordinary
     course of business, but including, without limitation, all liabilities
     created or arising under any conditional sale or other title retention
     agreement with respect to any such property);

               (c)  all liabilities appearing on its balance sheet in accordance
     with GAAP in respect of Capital Rentals under any Capitalized Lease;

               (d)  all liabilities for borrowed money secured by any Lien with
     respect to any property owned by such Person (whether or not it has assumed
     or become liable for such liabilities);

               (e)  all liabilities in respect of letters of credit or
     instruments serving a similar function issued or accepted for its account
     by banks or other financial institutions (whether or not representing
     obligations for borrowed money) ;

               (f)  the principal balance outstanding under any synthetic lease,
     tax retention operating lease, off-balance sheet loan or similar off-
     balance sheet financing product, including the ELLF and any Permitted Asset
     Securitization; and

               (g)  all Guaranties by such Person with respect to liabilities of
     the type described in (a) through (f) herein.

     Indebtedness of any Person shall include all obligations of such Person of
the character described in clauses (a) through (g) to the extent such Person
remains legally liable in respect thereof notwithstanding that any such
obligation is deemed to be extinguished under GAAP.

          (f)  The definition of "Priority Debt" is hereby amended and restated
in its entirety as follows:

               "PRIORITY DEBT" means the sum, without duplication, of (i)
     Indebtedness of the Company secured by Liens not otherwise permitted by
     clauses (a) through (i) of Section 10.5; and (ii) Indebtedness of
     Subsidiaries not otherwise permitted by clauses (a) through (c) of Section
     10.12 (but excluding the Indebtedness evidenced by the Subsidiary
     Guarantees); provided however, that the Indebtedness with respect to the
     ELLF shall not be deemed Priority Debt but any amendments, modifications,
     renewals, replacements or refinancings thereof shall constitute Priority
     Debt.

                                       3
<PAGE>

          (g)  The following new definition is hereby added to SCHEDULE B:

               "ELLF" means the Company's End Loaded Lease Facility as set forth
     in the Participation Agreement dated December 27, 1997 among the Company
     and the other parties thereto and as in effect on the effective date of the
     Amendment (with a maximum aggregate amount of $75,000,000) and without
     regard to any amendments, modifications, renewals, replacements or
     refinancings thereof.

          (h)  The parties acknowledge that the addbacks identified in item (c)
of the new definition of "Consolidated Income Available for Fixed Charges" shall
be considered nonrecurring items for purposes of calculating Consolidated
Operating Cash Flow.

     1.2  AMENDMENT TO SECTION 10.5.  SECTION 10.5 of each of the Note Purchase
Agreements is hereby amended by deleting the "and" at the end of clause (i),
replacing the "." at the end of clause (j) with "; and" and adding a new clause
(k) as follows:

          (k) Liens granted pursuant to the ELLF or any other tax retention
      operating lease or synthetic lease.

                                  ARTICLE 2.

                         REPRESENTATIONS AND WARRANTIES

     The Company hereby represents and warrants that:

     2.1  COMPLIANCE WITH NOTE PURCHASE AGREEMENTS. The Company is in compliance
with all terms and provisions set forth in the Note Purchase Agreements to be
observed or performed.

     2.2  REPRESENTATIONS IN NOTE PURCHASE AGREEMENTS.  The representations and
warranties of the Company set forth in the Note Purchase Agreements, except for
those relating to a specific date other than the date hereof, are true and
correct in all material respects on and as of the date hereof as if made on and
as of the date hereof.

     2.3  NO DEFAULT.  No Default or Event of Default is continuing.

     2.4  CONTINUING SECURITY INTERESTS. All amounts owing by the Company under
the Note Purchase Agreements and the Notes will continue to be secured by the
security interest in favor of the Collateral Agent on behalf of the Holders in
all of the collateral granted under the Security Documents and nothing herein
(other than the expressly permitted sharing of collateral with the Banks) will
affect the validity, perfection or enforceability of such security interests.

     2.5  NO CONFLICTS.  Neither the execution, delivery or performance of this
Amendment by the Company, nor compliance by the Company with the Note Purchase
Agreements as amended hereby, (a) conflicts or will conflict with or results or
will result in any breach of, or constitutes or will constitute with the passage
of time or the giving of notice or both, a default under, (i) any statute or
other rule or regulation of any Governmental Authority or (ii) any written or
oral agreement or instrument to which the Company or any of its Subsidiaries is
a

                                       4
<PAGE>

party or by which it, or any of its property, is bound, except where such
conflict, breach or default would not have a Material Adverse Effect, or (b)
results or will result in the creation or imposition of any lien, charge or
encumbrance upon the properties of the Company or any of its Subsidiaries
pursuant to any such agreement or instrument, except for Permitted Liens.

                                  ARTICLE 3.

                                    GENERAL

     3.1  EFFECTIVENESS. Upon satisfaction of the conditions set forth in
Section 3.10 below, this Amendment shall be effective as of December 31, 2000.

     3.2  MODIFICATION OF OTHER AGREEMENTS.  Any reference to the Note Purchase
Agreements in any of the Notes or Security Documents shall mean, unless
otherwise specifically provided, the Note Purchase Agreements as amended and
supplemented by this Amendment, and as the Note Purchase Agreements are further
amended, restated, supplemented or modified from time to time and any substitute
or replacement therefor or renewals thereof.

     3.3  CONSENT OF SUBSIDIARIES. This Amendment is expressly conditioned upon
the execution by each Guarantor of the Acknowledgement and Consent attached as
ANNEX 1 indicating such Guarantors' consent to this Amendment and confirming
their obligations pursuant to the Security Documents.

     3.4  FULL FORCE AND EFFECT.  As expressly amended hereby, the Note Purchase
Agreements shall continue in full force and effect in accordance with the
provisions thereof, and no change or modification in any of the terms thereof
except as specifically set forth herein has been effected.

     3.5  APPLICABLE LAW.  This Amendment shall be governed by and construed in
accordance with the internal laws and judicial decisions of the State of Texas.

     3.6  COUNTERPARTS. This Amendment may be executed in two or more
counterparts, each of which shall constitute an original, but all of which when
taken together shall constitute but one instrument.

     3.7  FEES, EXPENSES AND INDEMNITY. The Company will pay each Holder
executing this Amendment an upfront fee equal to 0.50% of the principal amount
of Notes held by such Holder on the date hereof. The Company agrees to pay all
out-of-pocket expenses incurred by the Holders in connection with the
preparation, execution and delivery of this Amendment, including, without
limitation, all reasonable attorneys' fees. The provisions of Section 16.1 of
the Note Purchase Agreements shall apply fully to this Amendment.

     3.8  FURTHER ASSURANCE. The Company shall execute and deliver to the
Holders such documents, certificates and opinions as the Holders may reasonably
request to effect the amendment contemplated by this Amendment.

     3.9  HEADINGS. The headings of this Amendment are for the purposes of
reference only and shall not affect the construction of this Amendment.

                                       5
<PAGE>

     3.10  CONDITIONS TO EFFECTIVENESS. This Amendment shall be effective as of
the date first set forth above upon (i) execution hereof by the Company and the
Required Holders, (ii) the delivery to the Holders of the fully-executed
Acknowledgement and Consent of the Guarantors, (iii) the payment of the fees
required by Section 3.7 hereof, and (iv) the prior or concurrent effectiveness
of an amendment to the Bank Loan Agreement (in form and substance satisfactory
to the Holders) amending the definitions and financial covenants therein to
include the equivalent exclusion from relevant financial covenant calculations
of the charges and expenses described in this Amendment.

             [the remainder of this page left blank intentionally]

                                       6
<PAGE>

     IN WITNESS WHEREOF, the Company and the Holders have executed this
Amendment as of the date hereof.

                              COMPANY:

                              US ONCOLOGY, INC.

                              By:  ___________________________________
                              Name:  _________________________________
                              Title: _________________________________

                              HOLDERS:

                              JOHN HANCOCK LIFE INSURANCE COMPANY
                              (formerly known as John Hancock Mutual Life
                              Insurance Company)

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                              JOHN HANCOCK VARIABLE LIFE
                              INSURANCE COMPANY

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                              INVESTORS PARTNER LIFE INSURANCE COMPANY

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                                       7
<PAGE>

                              THE NORTHERN TRUST COMPANY, as Trustee of the
                              Lucent Technologies, Inc. Master Pension Trust

                              By:  John Hancock Life Insurance Company,
                                   (formerly known as John Hancock Mutual Life
                                    Insurance Company), as Investment
                                    Manager

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                              ALLSTATE LIFE INSURANCE COMPANY

                              By: ____________________________________
                              Name: __________________________________

                              By: ____________________________________
                              Name: __________________________________
                                    Authorized Signatories

                              RELIASTAR LIFE INSURANCE COMPANY

                              By:  ING Investment Management LLC,
                                   as Agent

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                                       8
<PAGE>

                              RELIASTAR LIFE INSURANCE COMPANY OF
                              NEW YORK

                              By:  ING Investment Management LLC,
                                   as Agent

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                              SECURITY CONNECTICUT LIFE INSURANCE
                              COMPANY

                              By:  ING Investment Management LLC,
                                   as Agent

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                              CONNECTICUT GENERAL LIFE INSURANCE
                              COMPANY

                              By: CIGNA Investments, Inc.

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                              GENERAL ELECTRIC CAPITAL ASSURANCE
                              COMPANY

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                                       9
<PAGE>

                              FIRST COLONY LIFE INSURANCE COMPANY

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                              COLONIAL PENN INSURANCE COMPANY

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                              UNION FIDELITY LIFE INSURANCE
                              COMPANY

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                              MASSACHUSETTS MUTUAL LIFE
                              INSURANCE COMPANY

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                                       10
<PAGE>

                              C.M. LIFE INSURANCE COMPANY

                              By:  David L. Babson & Company Inc.
                                   Its Investment Sub-Advisor

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                              NATIONWIDE LIFE INSURANCE COMPANY

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                              NATIONWIDE LIFE AND ANNUITY
                              INSURANCE COMPANY

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                              OHIO NATIONAL LIFE INSURANCE COMPANY

                              By: ____________________________________
                              Name: __________________________________
                              Title:__________________________________

                                       11
<PAGE>

                                    ANNEX 1

                    ACKNOWLEDGMENT AND CONSENT OF GUARANTORS

                                 March 23, 2001

First Union National Bank, as Collateral Agent
One First Union Center
301 South College Street
Charlotte, North Carolina  28288-0735

RE:  AMENDMENT TO NOTE PURCHASE AGREEMENTS DATED AS OF MARCH 23, 2001 (THE
     "AMENDMENT"), BY AND AMONG US ONCOLOGY, INC. (THE "COMPANY") AND THE
     HOLDERS (THE "HOLDERS") OF THE COMPANY'S 8.42% SENIOR SECURED NOTES DUE
     NOVEMBER 2006

Ladies and Gentlemen:

     Each of the undersigned (individually, each "Guarantor," and collectively,
the "Guarantors") has either executed the Guaranty Agreement dated as of
November 24, 1999 or an Accession thereto (collectively, the "Guaranty"), in
favor of the Holders and for the benefit of the Company, guaranteeing the
Company's obligations under certain Note Purchase Agreements dated November 24,
1999 (as amended, the "Note Purchase Agreements").  Each Guarantor also has
either executed the Guarantors' Security Agreement dated as of November 24, 1999
or an Accession thereto (the "Security Agreement") pursuant to which each
Guarantor has granted to the Collateral Agent, for the benefit of the Holders, a
first priority security interest, subject to Permitted Liens, in all of the
Collateral described therein to secure its obligations under the Guaranty.

     Each Guarantor hereby acknowledges that the Company and the Holders have
amended the Note Purchase Agreements by the Amendment referenced above.  The
agreements of the Guarantors made herein are to induce the Holders to amend the
Note Purchase Agreements, and each Guarantor acknowledges that the Holders would
not amend the Note Purchase Agreement in the absence of the agreements of the
Guarantors contained herein.

     Each Guarantor hereby irrevocably approves of and consents to the
Amendment, agrees that its obligations under the Guaranty shall not be
diminished as a result of the execution of the Amendment, and ratifies and
confirms (i) that its obligations under the Guaranty shall include a guarantee
of the payment of the obligations of the Company under the Note Purchase
Agreements, the Notes and the Security Documents, subject to all of the
qualifications and limitations set forth therein, (ii) that such guarantee shall
be secured by the Collateral Agent's security interest in the Collateral granted
under the Guarantors' Security Agreement, and (iii) that the Guaranty, the
Guarantors' Security Agreement and all other loan documents to which such
Guarantor is a party shall remain in full force and effect.
<PAGE>

     Capitalized terms not defined herein shall have the meanings assigned to
such terms in the Note Purchase Agreements.

     This letter has been delivered in the State of Texas, and the agreements
contained herein shall be governed by the internal laws of the State of Texas,
without regard to the choice of law principles thereof.  The agreements
contained herein shall be effective as of the date hereof.

                              Very truly yours,

                              US ONCOLOGY CORPORATE, INC.
                              AORIP, INC.
                              AOR REAL ESTATE, INC.
                              AORT HOLDING COMPANY, INC.
                              AOR MANAGEMENT COMPANY OF ALABAMA, INC.
                              AOR MANAGEMENT COMPANY OF ARIZONA, INC.
                              AOR MANAGEMENT COMPANY OF FLORIDA, INC.
                              AOR MANAGEMENT COMPANY OF CENTRAL FLORIDA, INC.
                              AOR MANAGEMENT COMPANY OF INDIANA, INC.
                              AOR HOLDING COMPANY OF INDIANA, INC.
                              AOR MANAGEMENT COMPANY OF KANSAS, INC.
                              AOR MANAGEMENT COMPANY OF MISSOURI, INC.
                              AOR MANAGEMENT COMPANY OF NEVADA, INC.
                              AOR MANAGEMENT COMPANY OF NEW YORK, INC.
                              AOR MANAGEMENT COMPANY OF NORTH CAROLINA, INC.
                              AOR MANAGEMENT COMPANY OF OHIO, INC.
                              AOR MANAGEMENT COMPANY OF OKLAHOMA, INC.

                    [signatures continue on following page]

                                       2
<PAGE>

                              AOR MANAGEMENT COMPANY OF OREGON, INC.
                              AOR MANAGEMENT COMPANY OF PENNSYLVANIA, INC.
                              AOR MANAGEMENT COMPANY OF SOUTH CAROLINA, INC.
                              AOR MANAGEMENT COMPANY OF TEXAS, INC.
                              AOR MANAGEMENT COMPANY OF VIRGINIA, INC.
                              GREENVILLE RADIATION CARE, INC.
                              RMCC CANCER CENTER INC.
                              PHYSICIAN RELIANCE NETWORK, INC.
                              TOPS PHARMACY SERVICES, INC.
                              US ONCOLOGY RESEARCH, INC.
                              NORTHWEST CANCER CENTER, INC.
                              PRN PHYSICIAN RELIANCE, LLC
                              PHYSICIAN RELIANCE HOLDINGS, LLC
                              AOR OF TEXAS MANAGEMENT LIMITED PARTNERSHIP
                                    By:  AOR Management Company of Texas, Inc.,
                                         General Partner
                              AOR OF INDIANA MANAGEMENT PARTNERSHIP
                                    By:  AOR Management Company of Indiana,
                                         Inc., General Partner, and
                                    BY:  AOR HOLDING COMPANY OF INDIANA, INC.,
                                         GENERAL PARTNER
                              PHYSICIAN RELIANCE, L.P.
                                    By:  PRN Physician Reliance, LLC, General
                                         Partner and
                                    BY:  PHYSICIAN RELIANCE HOLDINGS, LLC,
                                         LIMITED PARTNER

                              By:  ____________________________________
                                    ________________, Manager of Physician
                                    Reliance Holdings, LLC and Treasurer of each
                                    other entity

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