<PAGE>   1
                                                                  EXHIBIT 10.19C

                    AMENDMENT TO STOCK OPTION AGREEMENT UNDER
                        THE DIRECTORS' STOCK OPTION PLAN

I.            Pursuant to Section 17.2 of the Guilford Pharmaceuticals Inc.
Directors' Stock Option Plan (the "Plan") the limitation on exercise of all
outstanding options granted under the Plan is modified and by adding new Section
3.6 of the Optionee's Stock Option Agreement to read as follows:

       3.6    VESTING UPON A CHANGE IN CONTROL

                     Notwithstanding any other provisions of the Plan or this
Agreement, in the event of a "Change in Control" (as defined below), any
unvested Options granted hereunder shall be accelerated and be fully vested as
of the date immediately prior to effective date of the Change in Control if the
Optionee continues to provide services to the Company as of the date of such
accelerated vesting. A "Change in Control" shall be deemed to have occurred if:

              (a)    any "person" (including, without limitation, any
individual, sole proprietorship, partnership, trust, corporation, association,
joint venture, pool, syndicate, or other entity, whether or not incorporated),
or any two or more persons acting as a syndicate or group or otherwise acting in
concert with regard to the ownership of securities of the Company and thereby
deemed collectively to be a "person") as such term is used in Sections 13(d) and
14(d) of the Securities Exchange Act of 1934, as amended (the "Exchange Act")),
becomes, after the date hereof, the "beneficial owner" (as defined in Rule 13d-3
under the Exchange Act), directly or indirectly, of securities of the Company
representing thirty percent (30%) or more of the combined voting power of the
Company's then outstanding securities, unless, in transaction in which a
"person" becomes, after the date hereof, the "beneficial owner" (as defined in
Rule 13d-3 under the Exchange Act), directly or indirectly, of securities of the
Company representing less than fifty percent (50%) of the combined voting power
of the Company's then outstanding securities, prior to the acquisition by such
person of securities of the Company which causes such person to have such
beneficial ownership, the full Board shall by at least a two-thirds vote have
specifically approved such acquisition and determined that such acquisition
shall not constitute a Change in Control for purposes of options granted under
the Plan despite such beneficial ownership; or

              (b)    during any two (2) year period, individuals who at the
beginning of such period constitute the Board, together with any new directors
elected or appointed during the period whose election or appointment resulted
from a vacancy on the Board caused by retirement, death , or disability of a
director and whose election or appointment was approved by a vote of at least
two-thirds (2/3rds) of the directors then still in office who were directors at
the beginning of the period, cease for any reason to constitute a majority
thereof.


<PAGE>   2



II.           Section 17 is added to each Optionee's Stock Option Agreement to
read as follows:


17.           CERTAIN ADDITIONAL PAYMENTS BY THE COMPANY.

              Notwithstanding any other provision of this Share Option Agreement
or of any other agreement, contract, or understanding heretofore or hereafter
entered into by the Optionee and the Company, except an agreement, contract, or
understanding hereafter entered into that expressly modifies or excludes
application of this Section 17 (the "Other Agreements"), and notwithstanding any
formal or informal plan or other arrangement heretofore or hereafter adopted by
the Company for the direct or indirect compensation of the Optionee (including
groups or classes of participants or beneficiaries of which the Optionee is a
member), whether or not such compensation is deferred, is in cash, or is in the
form of a benefit to or for an Optionee (a "Benefit Arrangement"), if the
Optionee is a "disqualified individual," as defined in Section 280G(c) of the
Code, in the event it shall be determined that any right to receive any payment
or other benefit under this Share Option Agreement, taking into account all
other rights, payments, or benefits to or for Optionee under the Plan, all Other
Agreements, and all Benefit Arrangements, would cause any payment or benefit to
an Optionee under this Plan to be considered a "parachute payment" within the
meaning of Section 280G(b)(2) of the Code as then in effect (a "Payment") which
would be subject to the excise tax imposed by Section 4999 of the Code or any
interest or penalties are incurred by the Optionee with respect to such excise
tax (such excise tax, together with any such interest and penalties, are
hereinafter collectively referred to as the "Excise Tax"), then the Optionee
shall be entitled to receive an additional payment (a "Gross-Up Payment") in an
amount such that after payment by the Optionee of all taxes (including any
interest or penalties imposed with respect to such taxes), including, without
limitation, any income taxes (and any interest and penalties imposed with
respect thereto) and Excise Tax imposed upon the Gross-Up Payment, the Optionee
retains an amount of the Gross-Up Payment equal to the Excise Tax imposed upon
the Payments.

              (b)    Subject to the provisions of Section 17(c), all
determinations required to be made under this Section, including whether and
when a Gross-Up Payment is required and the amount of such Gross-Up Payment and
the assumptions to be utilized in arriving at such determination, shall be made
by KPMG Peat Marwick or such other certified public accounting firm as may be
designated by the Optionee (the "Accounting Firm") which shall provide detailed
supporting calculations both to the Company and the Optionee within 15 business
days of the receipt of notice from the Optionee that there has been a Payment,
or such earlier time as is requested by the Company. In the event that the
Accounting Firm is serving as accountant or auditor for the individual, entity
or group effecting the Change of Control, the Optionee may appoint another
nationally recognized accounting firm to make the determinations required
hereunder (which accounting firm shall then be referred to as the Accounting
Firm hereunder). All fees and expenses of the Accounting Firm shall be borne
solely by the Company. Any Gross-Up Payment, as determined pursuant to this
Section, shall be paid by the Company to the


                                      - 2 -

<PAGE>   3


Optionee within five days of the receipt of the Accounting Firm's determination.
Any determination by the Accounting Firm shall be binding upon the Company and
the Optionee. As a result of the uncertainty in the application of Section 4999
of the Code at the time of the initial determination by the Accounting Firm
hereunder, it is possible that Gross-Up Payments which will not have been made
by the Company should have been made ("Underpayment"), consistent with the
calculations required to be made hereunder. In the event that the Company
exhausts its remedies pursuant to Section 17(c) and the Optionee thereafter is
required to make a payment of any Excise Tax, the Accounting Firm shall
determine the amount of the Underpayment that has occurred and any such
Underpayment shall be promptly paid by the Company to or for the benefit of the
Optionee.

              (c)    The Optionee shall notify the Company in writing of any
claim by the Internal Revenue Service that, if successful, would require the
payment by the Company of the Gross-Up Payment. The Optionee shall not pay such
claim prior to the expiration of the 30-day period following the date on which
it gives such notice to the Company (or such shorter period ending on the date
that any payment of taxes with respect to such claim is due). If the Company
notifies the Optionee in writing prior to the expiration of such period that it
desires to contest such claim, the Optionee shall:

                     (i)    give the Company any information reasonably
       requested by the Company relating to such claim,

                     (ii)   take such action in connection with contesting such
       claim as the Company shall reasonably request in writing from time to
       time, including, without limitation, accepting legal representation with
       respect to such claim by an attorney reasonably selected by the Company,

                     (iii)  cooperate with the Company in good faith in order
       effectively to contest such claim, and

                     (iv)   permit the Company to participate in any proceedings
       relating to such claim; provided,

however, that the Company shall bear and pay directly all costs and expenses
(including additional interest and penalties) incurred in connection with such
contest and shall indemnify and hold the Optionee harmless, on an after-tax
basis, for any Excise Tax or income tax (including interest and penalties with
respect thereto) imposed as a result of such representation and payment of costs
and expenses. Without limitation on the foregoing provisions of this Section
17(c), the Company shall control all proceedings taken in connection with such
contest and, at its sole option, may pursue or forgo any and all administrative
appeals, proceedings, hearings and conferences with the taxing authority in
respect of such claim and may, at its sole option, either direct the Optionee to
pay the tax claimed and sue for a refund or contest the claim in any permissible
manner, and the Optionee agrees to prosecute such contest to a determination


                                      - 3 -

<PAGE>   4


before any administrative tribunal, in a court of initial jurisdiction and in
one or more appellate courts, as the Company shall determine; provided, however,
that if the Company directs the Optionee to pay such claim and sue for a refund,
the Company shall advance the amount of such payment to the Optionee, on an
interest-free basis and shall indemnify and hold the Optionee harmless, on an
after-tax basis, from any Excise Tax or income tax (including interest or
penalties with respect thereto) imposed with respect to such advance or with
respect to any imputed income with respect to such advance; and further provided
that any extension of the statute of limitations relating to payment of taxes
for the taxable year of the Optionee with respect to which such contested amount
is claimed to be due is limited solely to such contested amount. Furthermore,
the Company's control of the contest shall be limited to issues with respect to
which a Gross-Up Payment would be payable hereunder and the Optionee shall be
entitled to settle or contest, as the case may be, any other issue raised by the
Internal Revenue Service or any other taxing authority.

              (d)    If, after the receipt by the Optionee of an amount advanced
by the Company pursuant to Section 17(c), the Optionee becomes entitled to
receive any refund with respect to such claim, the Optionee shall (subject to
the Company's complying with the requirements of Section 17(c)) promptly pay to
the Company the amount of such refund (together with any interest actually paid
or credited thereon after taxes applicable thereto). If, after the receipt by
the Optionee of an amount advanced by the Company pursuant to Section 17(c), a
determination is made that the Optionee shall not be entitled to any refund with
respect to such claim and the Company does not notify the Optionee in writing of
its intent to contest such denial of refund prior to the expiration of 30 days
after such determination, then such advance shall be forgiven and shall not be
required to be repaid and the amount of such advance shall offset, to the extent
thereof, the amount of Gross-Up Payment required to be paid.

                                    * * * * *




                                      - 4 -

<PAGE>   5


              IN WITNESS WHEREOF, the parties hereto have duly executed and
delivered this Amendment to Stock Option Agreement, or caused this Amendment to
Stock Option Agreement to be duly executed and delivered on their behalf, as of
the 17th day of August, 1998.



ATTEST:                                    GUILFORD PHARMACEUTICALS INC.


                                           By:
------------------------------------          ----------------------------------

                                           Title:
                                                 -------------------------------

                                           OPTIONEE:



                                           -------------------------------------







                                      - 5 -