bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of tumor estrogen and progesterone receptor levels on the response to tamoxifen and chemotherapy in primary breast cancer.
Authors: Fisher B , Redmond C , Brown A , Wickerham D L , Wolmark N , Allegra J , Escher G , Lippman M , Savlov E , Wittliff J
Published: February 2017

In 1977 the National Surgical Adjuvant Breast and Bowel Project initiated a prospectively randomized clinical trial for women with primary operable breast cancer and positive axillary nodes. In this study 1891 patients were randomized to receive L-phenylalanine mustard and 5-fluorouracil (PF) either with or without tamoxifen (T). In this interim report findings are presented concerning disease-free survival (DFS) and survival as related to age and to estrogen receptor (ER) and/or progesterone receptor (PR) content of the tumor. The median follow-up time is 3 yr. Patients 50 yr of age or older with either 1-3 or more than 3 positive axillary nodes had a markedly longer disease-free survival on PFT than did those receiving PF adjuvant therapy (p less than 0.001). The effectiveness of PFT was related to the levels of tumor receptors. Patients 50 yr old or more with both tumor ER and PR levels of 10 fmole or more ("high") displayed the greatest benefit in disease-free survival from PFT (p = 0.004). Analyses by age indicated that it is more appropriate to divide patients of 50 yr or older into two age groups, 50-59 and 60-70 yr old. In the former the survival results were poorer on PFT when tumor PR was low, whereas, regardless of receptor levels, those 60-70 yr old experienced an advantage on PFT. In women under 50 yr of age, there was no difference in disease-free survival (p = 0.64), but survival results favored the PF over the PFT treated (p = 0.06). Patients under 50 yr with tumor ER and PR levels under 10 fmole ("low") had a poorer survival when given PFT (p = 0.003). Those whose tumors demonstrated a high ER and a low PR also had a shorter survival on PFT (p = 0.01). The observation of no benefit in younger patients when both receptor levels were high, but a benefit in older patients with receptor-poor tumors, indicates that, at least according to the conditions of this study, the difference between the two age groups cannot be explained by the association of age with receptor content. Multivariate analyses considered the effects of the number of positive nodes, age, ER, and PR. They support the conclusion that, while nodes and ER exert strong prognostic influences in both PF- and PFT-treated patients, the PR content of tumors is a stronger predictor of the effectiveness of PFT therapy than is ER content.(ABSTRACT TRUNCATED AT 400 WORDS)
Trimethoprim/sulfamethoxazole versus placebo: a double-blind comparison of infection prophylaxis in patients with small cell carcinoma of the lung.
Authors: de Jongh C A , Wade J C , Finley R S , Joshi J H , Aisner J , Wiernik P H , Schimpff S C
Published: February 2017

The suppression of pathogenic aerobes and the preservation of anaerobes provides a degree of infection prevention during granulocytopenia. Trimethoprim/sulfamethoxazole (TMP/SMZ) suppresses Enterobacteriaceae and probably maintains colonization resistance through sparing of anaerobes. TMP/SMZ (320/1600 mg/day) treatment was compared to placebo in a double-blind, randomized trial in patients with newly diagnosed small cell carcinoma of the lung during the initial courses of chemotherapy with cyclophosphamide, doxorubicin, and etoposide. Infections were evaluated as microbiologically documented, with or without bacteremia, and clinically documented and were correlated to granulocytopenia. Of the 61 patients evaluated, 32 were given TMP/SMZ and 29 were given placebo; both groups had similar characteristics with regard to disease extent, performance status, age, sex, chemotherapy, and days of granulocytopenia. Incidence of infection at less than 100 granulocytes/microliters was significantly reduced in the TMP/SMZ group (2 infections/100 days) compared to placebo (11 infections/100 days, p = 0.005). Also reduced were the number of bacteremias and the mean proportion of study time on broad-spectrum antibiotics (p less than 0.01). Compared to placebo, TMP/SMZ provided infection prophylaxis without an increase in marrow suppression among patients with small cell carcinoma of the lung receiving intensive chemotherapy.
Combination chemotherapy for locally advanced pancreatic cancer: equivalence to external beam irradiation and implication for future management.
Authors: Smith F P , Stablein D , Korsmeyer S , Neefe J , Chun B K , Woolley P V , Schein P S
Published: February 2017

Chemotherapy with 5-fluorouracil, doxorubicin, and mitomycin-C was administered to 17 patients with locally advanced pancreatic cancer. The median survival for these patients was 8 months. With a multiaxial retrospective analysis, the overall survival of this study group appears to be least equivalent to that reported with 6,000 photon rad alone or of neutrons, and compares favorably to that achieved with combined 6,000 photo rad plus 5-fluorouracil. Of 15 relapses, only 4 had presented with evidence of disseminated disease. Based upon this analysis we recommend additional studies of combination chemotherapy with radiation therapy in future prospective randomized trials.
Treatment of acute lymphoblastic leukemia in adults: results of the L-10 and L-10M protocols.
Authors: Schauer P , Arlin Z A , Mertelsmann R , Cirrincione C , Friedman A , Gee T S , Dowling M , Kempin S , Straus D J , Koziner B
Published: February 2017

Two successive protocols (L-10 and L-10M) employing multidrug induction therapy with vincristine, prednisone, and doxorubicin (Adriamycin) plus an intensive consolidation phase and maintenance program have led to a significant improvement in the prognosis of adult acute lymphoblastic leukemia (ALL). The complete remission (CR) rates for the 34 patients entered on the L-10 protocol and the 38 patients entered on the L-10M protocol were 85% and 84%, respectively. The median duration of remission has not yet been reached for either the L-10 (median follow-up, 5.5 years; range, 3.5-7.5 years) or the L-10M protocol (median follow-up, 2.5 years; range, 1-3.5 years). The median survival time has not yet been reached for the L-10M protocol. Central nervous system prophylaxis with intrathecal methotrexate alone was effective in preventing central nervous system relapse. An analysis of possible prognostic factors indicated that patients less than 25 years of age had a higher CR rate than older patients (p = 0.02). Patients with an initial leukocyte count below 15,000/microL experienced longer remissions than patients with a leukocyte count above 15,000/microL (p = 0.008), and patients who achieved CR within the first month of therapy were in remission longer than those requiring a longer time to achieve CR (p = 0.04). Patients with T cell ALL did not have a poorer prognosis than other patients treated on these protocols. The L-10 and L-10M protocols were well tolerated with minimal morbidity.
Weekly doxorubicin in endocrine-refractory carcinoma of the prostate.
Authors: Torti F M , Aston D , Lum B L , Kohler M , Williams R , Spaulding J T , Shortliffe L , Freiha F S
Published: February 2017

Twenty-five patients with endocrine-refractory prostatic carcinoma were treated with doxorubicin, 20 mg/m2 given weekly. All patients had prior hormonal therapy (68% had two or more prior hormonal maneuvers), and 21 (84%) had prior therapeutic or palliative irradiation. Median Karnofsky performance status at the time of entry was 70. Hemoglobin was less than 12.0 g/dL in 15 patients. Bidimensional tumors were present in 12 patients in 19 disease sites; four of the 12 patients (33%) responded in eight of the 19 sites (42%); and three of eight patients had a 75% decrease in prostatic nodule size. Ten of 20 evaluable patients had an improvement of 20% or greater in Karnofsky performance status and 67% (14 of 21) had marked improvement in pain. A greater than 50% reduction or normalization of acid phosphatase occurred in 19% and of alkaline phosphatase in 53%. The overall response rate by National Prostatic Cancer Project criteria was 84%. Gastrointestinal toxicity and alopecia were minimal and myelosuppression was not life threatening in any patient.
Human tumor cell heterogeneity and metastasis.
Authors: Spremulli E N , Dexter D L
Published: February 2017

Heterogeneity within malignant neoplasms, although described for many years by pathologists, has only recently been extensively studied in the laboratory. It is now accepted that most tumors are composed of subpopulations of cells that differ in many phenotypic characteristics including the ability to form a metastasis. Cells with the capacity to metastasize are the ones most likely to prove lethal to the patient since clinicians can often control the primary neoplasm with surgery or radiotherapy. In this report the process of metastasis is discussed, those aspects of tumor cell heterogeneity that are relevant to this process are reviewed, intrapatient tumor heterogeneity is explored, and future preclinical studies are evaluated that may be useful in designing treatment strategies for patients with disseminated malignancies.
Karnofsky Memorial Lecture. Marrow transplantation for malignant diseases.
Authors: Thomas E D
Published: February 2017

Marrow grafting, once undertaken only after failure of all other forms of therapy, is now the preferred therapy for some malignant diseases. Chemoradiotherapy and marrow grafting for patients with acute leukemia who have failed chemotherapy results in cure rates of 10%-30%. For patients under the age of 50 with acute nonlymphoblastic leukemia transplanted in first remission, the cure rate is approximately 50% with better results in younger patients. Marrow grafting is now being explored in a variety of types of malignant diseases having in common a steep dose-response curve to therapy, therapy limited by marrow toxicity, and the availability of a suitable marrow donor. Current research in the field of marrow transplantation is reviewed and provides a basis for a reasonable expectation that results of marrow transplantation will continue to improve. The use of partially matched family members or phenotypically histocompatibility leukocyte antigen-identical unrelated donors will make marrow grafting available to a larger fraction of patients. Marrow grafting, developed for the treatment of malignant disease, has found an important application to nonmalignant diseases, including immunodeficiency syndromes, aplastic anemia, and thalassemia and other genetic disorders of hematopoiesis.
Outcome following late marrow relapse in childhood acute lymphoblastic leukemia.
Authors: Chessells J , Leiper A , Rogers D
Published: February 2017

Thirty-four children with acute lymphoblastic leukemia, who developed bone marrow relapse after treatment was electively stopped, received reinduction, consolidation, continuing therapy, and intrathecal (IT) methotrexate (MTX). Sixteen children who relapsed within six months of stopping treatment had a median second-remission duration of 26 weeks; all next relapses occurred in the bone marrow. In 18 children who relapsed later, the median duration of second remission was in excess of two years, but after a minimum of four years' follow-up, 16 patients have so far relapsed again (six in the CNS). CNS relapse occurred as a next event in four of 17 children who received five IT MTX injections only and in two of 14 children who received additional regular IT MTX. Although children with late marrow relapses may achieve long second remissions, their long-term out-look is poor, and regular IT MTX does not afford adequate CNS prophylaxis. It remains to be seen whether more intensive chemotherapy, including high-dose chemoradiotherapy and bone marrow transplantation, will improve the prognosis in this group of patients.
Treatment of epidemic Kaposi's sarcoma with etoposide or a combination of doxorubicin, bleomycin, and vinblastine.
Authors: Laubenstein L J , Krigel R L , Odajnyk C M , Hymes K B , Friedman-Kien A , Wernz J C , Muggia F M
Published: February 2017

An epidemic of disseminated Kaposi's sarcoma in male homosexuals has recently been described. Forty-one evaluable patients with epidemic Kaposi's sarcoma were treated with etoposide. The majority of these patients had early stage disease, no prior opportunistic infections, and no prior therapy. Twelve patients (30%) achieved complete remission, 19 (46%) partial remission, and ten (24%) no response. With follow-up time to 31 months, the median response duration is nine months. The median survival of patients with complete and partial remissions has not been reached. A combination of doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), bleomycin, and vinblastine (ABV) was used in 31 evaluable patients with epidemic Kaposi's sarcoma. The majority of these patients had late stage disease, prior opportunistic infections, or had failed prior treatment. Seven patients (23%) achieved complete remission, 19 (61%) partial remission, and five (61%) no response. With follow-up time to 24 months, the median response duration is eight months. The projected median survival for all patients treated with ABV is nine months. Both regimens were well tolerated, with an overall response rate of 76% for etoposide and 84% for ABV. However, while successfully treating the Kaposi's sarcoma, the underlying immune deficiency in these patients has persisted. Future treatments of Kaposi's sarcoma will need to focus on reversing the underlying immune incompetence as well as controlling the malignant manifestations of Kaposi's sarcoma arising in relation to the acquired immune deficiency syndrome.
Radiation therapy in the treatment of meningioma: the Joint Center for Radiation Therapy experience 1970 to 1982.
Authors: Forbes A R , Goldberg I D
Published: February 2017

The standard treatment for meningioma is complete resection. However, complete resection is often not possible because of tumor location and extent. To evaluate the usefulness of radiation therapy in patients with unresected or residual tumor, we reviewed the Joint Center for Radiation Therapy experience from 1970 to 1982 (n = 31). Histologic diagnosis was available in 27 patients. The patients were treated with megavoltage radiation to a mean dose of 5,280 rad (3,780 to 6,050 rad) in 180- to 200-rad daily fractions using multiple static or rotational fields. The median follow-up period was 45 months, with a range of four to 156 months. The overall four-year relapse-free survival (RFS) rate was 72%. All relapses occurred within the first 37 months; the mean time to relapse was 31 months. The four-year RFS was the same whether patients were treated at initial presentation or after recurrence (74% v 67%, respectively). There was no difference in RFS for patients treated after partial resection or those patients with no resection (76% v 64%). No patients with malignant meningioma were relapse free three years after radiation therapy. Complications included decreased auditory acuity in three patients and retinopathy in one patient. These data suggest that moderate dose radiation therapy can offer long-term symptom-free survival with few complications in patients having unresected or partially resected benign meningioma.
VP-16-213 in combination chemotherapy with chest irradiation for small-cell lung cancer: a randomized trial of the Piedmont Oncology Association.
Authors: Jackson D V , Zekan P J , Caldwell R D , Slatkoff M L , Harding R W , Case L D , Hopkins J O , Muss H B , Richards F , White D R
Published: February 2017

The role of etoposide epipodophyllotoxin (VP-16-213) in a combined modality treatment program incorporating local chest irradiation and combination chemotherapy with cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, Ohio), and vincristine has been evaluated in a randomized trial of 165 patients with small-cell lung cancer. The overall response rate (complete response [CR] plus partial response [PR]) was significantly greater in the VP-16-213 arm (85% v 64%, P = .005) primarily as a consequence of improved response in patients with extensive disease (85% v 38%, P = .002 and 30% v 8% for CR only, P = .045). No differences in the response rates were observed in limited disease. The duration of response (months) was greater in the VP-16-213 arm (8.6 v 7.0 overall and 14.4 v 11.5 for CR) but not significantly so. Median survival times (months) were consistently greater in the group receiving VP-16-213 when analyzed according to extent of disease and response (10.6 v 9.5 overall; 15.0 v 13.6 for limited disease; 9.0 v 6.7 for extensive disease; 18.5 v 16.2 for CR overall; and 18.6 v 16.1 for CR in limited disease); the results were not statistically significant. The median survival of extensive disease patients attaining a CR was 15.3 months (range 3.2 to 34.3 + months) in the VP-16-213 arm and 7.4+ and 8.1+ months for the two patients with CR in the other group. Anemia and leukopenia occurred to a greater degree in the four-drug regimen, but no unusual or significant compounding toxicity (ie, neurotoxicity) was observed otherwise. Further investigation of this agent in combination chemotherapy programs for small-cell lung cancer appears to be warranted.
An Eastern Cooperative Oncology Group evaluation of combinations of methyl-CCNU, mitomycin C, Adriamycin, and 5-fluorouracil in advanced measurable gastric cancer (EST 2277).
Authors: Douglass H O , Lavin P T , Goudsmit A , Klaassen D J , Paul A R
Published: February 2017

In a prospectively randomized trial, patients with advanced locally recurrent or metastatic gastric adenocarcinoma were randomized to receive 5-fluorouracil (5-FU) and methyl-CCNU; 5-FU, Adriamycin (Adria Laboratories, Columbus, Ohio), and methyl-CCNU; 5-FU, Adriamycin, and mitomycin C; or Adriamycin and mitomycin C alone. One hundred eighty-three previously untreated evaluable patients were randomized among the four arms. An additional 39 patients previously treated with 5-FU, were assigned to treatment directly to Adriamycin and mitomycin C. Response rates were 14%, 29%, 39%, and 29%, respectively, among previously untreated patients and 21% for Adriamycin and mitomycin C among previously treated patients. 5-Fluorouracil, Adriamycin, and mitomycin C, the arm containing the largest number of responders (18), was the combination associated with the longest median survival. A larger proportion of patients in this arm survived one year or more. In addition, the 5-FU, Adriamycin, and mitomycin C program had the lowest rate of severe or worse toxicity of any of the treatments and was effective in patients who were less than fully ambulatory and in those who had lost weight. 5-Fluorouracil, Adriamycin, and mitomycin C appear to be a likely combination to be considered in a surgical adjuvant program.
Randomized phase III trial of vinblastine, bleomycin, and cis-dichlorodiammine-platinum versus dacarbazine in malignant melanoma.
Authors: Luikart S D , Kennealey G T , Kirkwood J M
Published: February 2017

A randomized phase III study was carried out in 57 patients with metastatic melanoma treated with either dacarbazine (DTIC) given intravenously (IV) daily for 10 days using light protection, or a combination of vinblastine IV on days 1 and 2, bleomycin by continuous IV infusion during days 1-5, and cisplatin by IV infusion on day 5 (VBD). Objective response rates were similar: 14% for dacarbazine and 10% for VBD. However, dacarbazine responses were associated with a trend toward longer progression-free intervals and longer survival. Toxicity was significantly greater in the VBD arm, and fatal in two patients. Dacarbazine was also associated with severe toxicity by the 10-day light-protected schedule used here. VBD is not as effective as previously reported, and dacarbazine remains a standard of therapy for metastatic melanoma.
Karnofsky performance status revisited: reliability, validity, and guidelines.
Authors: Schag C C , Heinrich R L , Ganz P A
Published: February 2017

Little research has been conducted documenting the reliability and validity of the Karnofsky Performance Status (KPS) scale, and guidelines based on empirical data do not exist to govern its use. Two hundred ninety-three cancer patients completed a questionnaire that assesses their physical and psychosocial difficulties. Physicians rated patients on the KPS and a subsample of 75 patients was used to evaluate interrater reliability. Analyses were conducted to evaluate the interrater reliability and construct validity of the KPS. The KPS was shown to have good reliability and validity. Detailed examination of the reliability data suggested areas in which physicians err in their judgments. Multiple regression techniques were used to empirically identify seven behaviorally based questions that would be helpful in predicting KPS scores. The seven variables included weight loss, weight gain, reduced energy, difficulty walking, driving, grooming, and working part time. An interview approach with behaviorally based guidelines is presented using these variables to obtain relevant data and make more accurate KPS ratings. With the approach suggested and the guidelines presented, oncologists may train themselves to use the KPS in a standard way, which should increase reliability and validity of the KPS and has implications for patients and research studies that use KPS as a stratifying variable.
Orchiectomy alone in the treatment of clinical stage I nonseminomatous germ cell tumor of the testis.
Authors: Sogani P C , Whitmore W F , Herr H W , Bosl G J , Golbey R B , Watson R C , DeCosse J J
Published: February 2017

Forty-five patients with clinical stage I nonseminomatous germ cell tumor of the testis (NSGCTT) were entered in a prospective clinical trial to receive no treatment other than orchiectomy until clinical evidence of relapse. Of this group, 36 patients (80%) have been continuously free of disease for a median duration of 19.5 months after orchiectomy. Nine patients (20%) have relapsed, eight within seven months of orchiectomy. Seven of nine relapsing patients have been rendered free of disease with chemotherapy and/or surgery for a median duration of seven months (range, one to 33 months) after completion of treatment; the other two patients are presently under treatment although one has progressive disease. The relapse rate was higher in patients with embryonal carcinoma than in those with teratocarcinoma, 57% versus 17%. These preliminary results imply that the omission of routine lymphadenectomy or lymph-node irradiation in clinical stage I NSGCTT deserves further trial.
Drug combinations in the treatment of gastric adenocarcinoma: a randomized Southwest Oncology Group study.
Authors: Panettiere F J , Haas C , McDonald B , Costanzi J J , Talley R W , Athens J , Oishi N , Heilbrun L K , Chen T T
Published: February 2017

The FAM combination with the simultaneous administration of 5-fluorouracil, doxorubicin, and mitomycin C is considered standard chemotherapy for gastric adenocarcinoma. This study was initiated to determine whether a kinetically designed sequential administration of these three drugs would be superior and whether the presence or absence of easily measurable tumor would imply differences in survival. To do so, the Southwest Oncology Group tested two schedules in a randomized study of 239 patients. Independent judgments of response were made by two authors with the same results. Equivalent response rates (23% of all eligible sequential and 30% simultaneous) and median survival durations (22 and 23 weeks, respectively) were seen. Patients with and without readily measurable tumors each lived a median of 22 weeks. Higher degrees of hematologic toxicity were associated with prolonged survival (median 27 weeks versus 20 weeks, p = 0.04). Patients treated by community oncologists were described as having higher response rates than those treated in major medical centers (64% versus 31%, p = 0.03). The meaning of this is questionable in that there were no statistical differences in survival or toxicity. Those with prior exposure to 5-fluorouracil had only a tendency, without statistical significance, for a slightly inferior response and survival.
Prognostic significance of complete surgical resection of pulmonary metastases in patients with osteogenic sarcoma: analysis of 32 patients.
Authors: Goorin A M , Delorey M J , Lack E E , Gelber R D , Price K , Cassady J R , Levey R , Tapper D , Jaffe N , Link M
Published: February 2017

Between 1972 and 1981, 93 patients with extremity osteogenic sarcoma without detectable metastatic disease were treated with surgery and adjuvant chemotherapy. Fifty-two patients remain continuously free of disease. Thirty-two of the 41 patients who relapsed had pulmonary metastases only and 26 underwent thoracotomy to remove all metastatic disease. Complete resection was possible in 11 of 26 patients as defined by the removal of all macroscopic disease, no microscopic disease at resection margins, and no histologic evidence of pleural disruption by tumor. Nine of 11 patients are currently free of disease with a median duration of most recent remission of 42 months (range, 3-72 months). Four of these nine patients have had only one relapse. Only two of 15 patients with incomplete resection of metastatic disease defined by the above criteria are currently free of disease for 57 and 101 months. A significant difference in survival from initial relapse for patients made surgically free of disease using this stringent criteria was observed even when the result is stratified for time to first relapse and number of pulmonary nodules (p = 0.005). A subgroup of patients within the group undergoing thoracotomies who can be expected to have an improved survival has been defined.
Double-blind crossover study of the antiemetic efficacy of high-dose dexamethasone versus high-dose metoclopramide.
Authors: Aapro M S , Plezia P M , Alberts D S , Graham V , Jones S E , Surwit E A , Moon T E
Published: February 2017

Nausea and vomiting remain common and debilitating side effects of therapy with many anticancer drugs. Recent reports have shown that both metoclopramide and dexamethasone are effective drugs for the treatment of severe nausea and vomiting caused by cis-platinum. A double-blind crossover study comparing the antiemetic properties of high-dose oral and intravenous regimens of metoclopramide and dexamethasone in outpatients was carried out. Standardized patient questionnaires and interviews were used to evaluate response. Dexamethasone and metoclopramide protected against more than five episodes of emesis in 48% and 40% of patients, respectively. Nausea persisted for less than six hours in 45% of patients on dexamethasone and in 37% on metoclopramide. The antiemetic efficacy of both regimens was retained through repeated courses of chemotherapy. Side effects were minimal with dexamethasone; however, 33% of patients experienced unacceptable extrapyramidal side effects to metoclopramide. Patient preference was significantly in favor of dexamethasone: 70% of patients chose to continue dexamethasone compared to 22% who preferred metoclopramide and 8% who chose other antiemetics. Dexamethasone was the preferred antiemetic in this patient population due to minimal side effects.
Methodologic issues in trials of antiemetics.
Authors: Pater J L , Willan A R
Published: February 2017

Studies of antiemetics require consideration of methodologic issues that may not be of concern in trials of antineoplastics. This paper illustrates how the strength of the results of these studies can be affected by (1) the types of patients studied, (2) the sample size, (3) the trial design, (4) the choice and definition of outcome measures, and (5) the method of analysis.
Preliminary results of a randomized trial of adjuvant doxorubicin for sarcomas: lack of apparent difference between treatment groups.
Authors: Antman K , Suit H , Amato D , Corson J , Wood W , Proppe K , Harmon D , Carey R , Greenberger J , Blum R
Published: February 2017

Forty-two patients with localized intermediate and high-grade sarcoma were randomized after optimal primary treatment to receive five cycles of adjuvant doxorubicin 90 mg/m2 every three weeks (20 patients) or observation (22 patients). Patients were stratified for grade, size, extent of surgical margin, and soft tissue versus other sarcomas. Groups appeared balanced for histology and superficial versus deep lesions. Eight patients (19%) have died. Follow-up times range from two to 69 months (median, 16 months). Two patients receiving doxorubicin (10%) developed cardiotoxicity presenting as pulmonary edema. One patient returned to normal activity on digoxin and diuretics; the other (age, 28 years) died of intractable failure and arrhythmias after four weeks. While a nonsignificant difference in local control, metastasis-free survival, disease-free survival, and survival was observed for extremity lesions, the advantage may be outweighed by the risk of cardiotoxicity. Seventy-six percent of the control patients with extremity lesions remain disease free. Because control patients do well, a very large study is required to define the role of adjuvant doxorubicin.
Peripheral T-cell lymphoma: a clinicopathologic study of 42 cases.
Authors: Greer J P , York J C , Cousar J B , Mitchell R T , Flexner J M , Collins R D , Stein R S
Published: February 2017

Clinical and histopathologic material from 42 patients with peripheral T-cell lymphoma (PTCL) was reviewed. The median age was 63.5 years (range, 11-97 years). The male:female ratio was 2.8:1. Prior immune or lymphoproliferative diseases occurred in 36% of the patients. PTCL was advanced at presentation with B symptoms (67%), generalized adenopathy (69%), and stage III/IV disease (79%). Suspected lung or pleural involvement (21%), hepatomegaly (29%), and splenomegaly (43%) were common; marrow involvement was documented in 37% of the patients at presentation and in 51% of patients during the illness. Hypercalcemia and eosinophilia occurred in 19% and 29% of patients, respectively. Among patients receiving combination chemotherapy (BCOP, CHOP, BACOP, COMLA), eight (24%) of 33 achieved a complete remission and only four (12%) of 33 had a sustained complete remission. The median survival for PTCL was 11 months. Because of the poor response to standard therapy, clinical trials should identify cases of PTCL and evaluate newer regimens in this subset of aggressive lymphoma.
Improved prognosis for infants with stage IV neuroblastoma.
Authors: Kretschmar C S , Frantz C N , Rosen E M , Cassady J R , Levey R , Sallan S E
Published: February 2017

From 1970 to 1982 11 infants with Evans stage IV neuroblastoma who were 11 months of age or less at diagnosis were treated. All but one were treated with intensive multiagent chemotherapy; eight had attempted surgical resection; only one received radiotherapy to the primary tumor. Ten of the 11 infants remain free of disease from 2 1/2 to 13 years (median, four years). Multiagent chemotherapy has clearly improved the outcome for infants with stage IV neuroblastoma.
The role of radiation therapy in the management of stage III follicular lymphomas.
Authors: Paryani S B , Hoppe R T , Cox R S , Colby T V , Kaplan H S
Published: February 2017

Between 1961 and 1982, 66 patients with stage III follicular small cleaved (FSC) and follicular mixed small cleaved and large cell (FM) lymphoma were treated at Stanford University. Treatment consisted of total-lymphoid irradiation (TLI) to a total dose of about 4,000 rad in 61 patients or whole-body irradiation (WBI) followed by boost irradiation to sites of involvement in five patients. In addition, 13 patients treated with TLI received adjuvant chemotherapy, consisting of six cycles of cyclophosphamide, vincristine, and prednisone (CVP). Median follow-up was 9.6 years. Kaplan-Meier actuarial survival at five, ten, and 15 years was 78%, 50%, and 37%, respectively. Freedom from relapse at five and ten years was 60% and 40% with no relapses after ten years. In a prospective randomized study of 16 patients who all underwent staging laparotomy comparing TLI with or without adjuvant chemotherapy with CVP, there was no significant difference in either survival or freedom from relapse between the two groups. Patients with limited stage III disease (without B symptoms, less than five sites of involvement, and maximum size of disease less than 10 cm) had an excellent prognosis with a 15-year survival and freedom from relapse of 100% and 88%, respectively. Radiation therapy may be a potentially curative modality in patients with stage III follicular lymphomas.
Full dose versus attenuated dose daunorubicin, cytosine arabinoside, and 6-thioguanine in the treatment of acute nonlymphocytic leukemia in the elderly.
Authors: Kahn S B , Begg C B , Mazza J J , Bennett J M , Bonner H , Glick J H
Published: February 2017

Between July 1, 1981 and November 1, 1982, 45 patients with acute nonlymphocytic leukemia (age, greater than or equal to 70 years) were randomly assigned to receive induction chemotherapy using either daunorubicin, cytosine arabinoside, and 6-thioguanine in full dosage (F DAT) or an attenuated schedule of the same drugs (At DAT) as part of an Eastern Cooperative Oncology Group controlled trial. Forty patients were deemed evaluable, 20 on each arm. The overall complete remission (CR) rate for all patients in both arms was 28% (11/40). There was no significant difference in CR rates between the two arms. There were 12 early deaths (less than 60 days) in the F DAT arm compared with only five early deaths on the At DAT arm (P = .05). Due primarily to this early death rate, the median survival for the F DAT group was 29 days v 159 days for the At DAT groups (P = .02). The range of survival of the patients in CR for the At DAT group given either one or two cycles of induction therapy was 121 to 414 days, while the survival range for the F DAT CR patients was 121-186 + days. The median survival for those not achieving CR was 14 days for the F DAT group v 80 days for the At DAT (P less than .02). Fifty-nine percent of the At DAT patients spent greater than 100 days out of the hospital v 12% for the F DAT group. Attenuated chemotherapy with lower doses of DAT is the preferred induction regimen for elderly patients with acute nonlymphocytic leukemia since it causes fewer early deaths, allows a better quality of life, and yields survival times as durable as intensive therapy.
Long-term remission durability and functional status of patients treated for diffuse histiocytic lymphoma with the CHOP regimen.
Authors: Armitage J O , Fyfe M A , Lewis J
Published: February 2017

Thirty-eight (51%) of 75 patients treated with CHOP for diffuse histiocytic lymphoma achieved complete remission. Twenty-three of the complete responders are currently alive in complete remission 24-78 months (median, 38 months) after discontinuing therapy. Eleven patients died from recurrent lymphoma and four patients died in complete remission from other causes. Evaluation of the 23 patients alive in complete remission found them mostly well and without serious sequelae to therapy. Comparison with 20 patients who were in the same age range, were disease free after surgery, and had no other therapy for colon cancer revealed only an increased frequency of sexual dysfunction in the chemotherapy-treated lymphoma patients. Sixty-one percent of patients who achieved complete remission with the CHOP regimen are long-term disease-free survivors and are generally well except for an apparently high frequency of sexual dysfunction.
Influence of place of treatment on diagnosis, treatment, and survival in three pediatric solid tumors.
Authors: Kramer S , Meadows A T , Pastore G , Jarrett P , Bruce D
Published: February 2017

This study examines differences between cancer centers (CC) and noncancer centers (NCC) in terms of management procedures and outcomes for three pediatric solid tumors: Wilms' tumor (N = 147), rhabdomyosarcoma (N = 87), and medulloblastoma (N = 76). Data were derived for the period 1970-1979 from the population-based Greater Delaware Valley Pediatric Tumor Registry maintained at the Children's Cancer Research Center, which routinely collects data on all childhood neoplasms that occur in a 31-county region. Management measures reviewed included the degree to which important pretreatment evaluations were performed, types of therapy used, and extent of follow-up examinations conducted. Outcome variables were three-year disease-free survival and frequency of deaths related to complications of therapy. Differences in three-year disease-free survival between CC and NCC were noted for medulloblastoma (52% v 24%) and rhabdomyosarcoma (48% v 10%), but not for Wilms' tumor (79% v 68%). Among medulloblastoma patients, differences were detected in the frequency of pretreatment evaluations and in the therapy used. The principal management contrast found in rhabdomyosarcoma was that multiagent chemotherapy was used less often in NCC. Wilms' tumor patients were evaluated and treated similarly in the community versus the CC, except for some contrasts in the surgical approach and the frequency of follow-up for the detection of late complications.
Lymphokine-activated human blood monocytes destroy tumor cells but not normal cells under cocultivation conditions.
Authors: Fidler I J , Kleinerman E S
Published: February 2017

The possibility that tumoricidal human blood monocytes would recognize and destroy tumorigenic targets but leave bystander nontumorigenic cells unharmed was investigated. Highly purified preparations of peripheral blood monocytes isolated from normal human donors were activated in vitro by incubation with human lymphokines encapsulated in multilamellar liposomes. The cytotoxic properties of these monocytes against several tumorigenic and nontumorigenic allogeneic target cell populations were assessed by an in vitro radioisotope-release assay. Various combinations of three tumorigenic and three nontumorigenic target-cell populations, labeled with either [3H]thymidine or [14C]thymidine, were mixed and plated onto monolayers of blood monocytes. In all combinations used, activated monocytes specifically lysed only allogeneic neoplastic cells. At least in vitro, activated human blood monocytes can recognize and selectively destroy neoplastic cells.
A proposal for the addition of hyperthermia to treatment regimens for acute and chronic leukemia.
Authors: Robins H I , Dennis W H , Steeves R A , Sondel P M
Published: February 2017

The application of hyperthermia to the treatment of neoplastic disease has focused on solid tumors. Human leukemias, both acute and chronic, may represent a unique category of diseases for which hyperthermia should be used in combination with other modalities with curative intent. Three clinical approaches to include hyperthermia are proposed. These are hyperthermia in combination with therapeutic low-dose whole-body irradiation, ablative high-dose total body irradiation, and bone marrow transplantation with the in vitro use of hyperthermia to purge remission bone marrow of abnormal cells. Current preclinical research further supporting these clinical applications of hyperthermia to leukemia therapy is presented.
A follow-up of a randomized study comparing two chemotherapy treatments for advanced diffuse histiocytic lymphoma.
Authors: Todd M , Cadman E , Spiro P , Bertino J , Farber L , Waldron J , Fischer D
Published: February 2017

In 1976 we began a randomized study for the treatment of patients with stage III and IV diffuse histiocytic lymphoma. The therapy was either ACOMLA (doxorubicin, cyclophosphamide, vincristine [oncovin], methotrexate with leucovorin rescue, and cytarabine) or CHOP-B (cyclophosphamide, doxorubicin [hydroxydaunorubicin], vincristine [oncovin], prednisone, and bleomycin). A complete response (CR) was achieved in 13 (65%) of 20 patients treated with ACOMLA and in 20 (71%) of the 28 patients treated with CHOP-B. Four patients achieving CR with ACOMLA and three patients treated with CHOP-B have relapsed for an overall relapse rate of 21%. Partial response (PR) was obtained in four patients treated with ACOMLA and five patients treated with CHOP-B. Median follow-up time is 36 months for the combined treatment groups. Multiple regression analysis demonstrated that those patients who were classified by the Lukes-Collins criteria as having histiocytic lymphoma not of follicular center-cell origin (combined T- and B-cell immunoblastic sarcoma) had a significantly worse survival as compared to patients classified with follicular center-cell origin lymphoma (large cell noncleaved, large cell cleaved, and large cell unclassified) with a 40% five-year survival versus an 80% five-year survival (P = .011). The CR rate however for these two large categories of patients was 63% v 73% respectively, and the relapse rates were equivalent. The increased survival in the follicular center-cell origin lymphomas may be related to a longer survival of PRs and relapsed patients as compared to the patients with nonfollicular center-cell lymphomas.
Abnormal computed tomography brain scans in children with acute lymphoblastic leukemia: serial long-term follow-up.
Authors: Riccardi R , Brouwers P , Di Chiro G , Poplack D G
Published: February 2017

In a previous study we reported the occurrence of computed tomographic (CT) brain-scan abnormalities in a group of asymptomatic children with acute lymphoblastic leukemia (ALL) who had received prophylactic cranial irradiation and maintenance intrathecal chemotherapy. One or more of four types of CT-scan abnormalities were observed: ventricular dilatation (VD), subarachnoid space dilatation (SAD), areas of parenchymal decreased attenuation coefficient (DAC), and intracerebral calcifications (CALs). To study the natural history of these findings, serial CT scans were obtained on 24 of the original 32 patients who were available for long-term follow-up. CT scanning was performed for a minimum of seven years from the initiation of CNS preventive therapy. Review of the CT scans showed that VD (n = 5) and SAD (n = 7) were stable over the time of follow-up. DAC, originally observed in two patients, was no longer present on follow-up scans. In contrast, five patients developed CALS from five to seven years after initiation of CNS preventive therapy. All occurred in children who were less than 8 years of age at the time of diagnosis (P less than .01). These data indicate that CALs may develop many years after the cessation of CNS preventive therapy and suggest that long-term CT-scan follow-up should be considered in children who have received CNS preventive therapy.
Phase I trial of misonidazole (NSC#261037) plus cyclophosphamide in solid tumors.
Authors: Davila E , Klein L , Vogel C L , Johnson R , Ostroy F , Browning S , Gorowski E , Furner R L , Presant C A
Published: February 2017

Misonidazole, a hypoxic cell sensitizer, enhances the antitumor effects of cyclophosphamide in preclinical studies. Several studies also showed increased cytotoxicity for normal tissues. We undertook a phase I study of this combination. The regimen consisted of oral administration of misonidazole at one of two dose levels, 1 g/m2 and 2 g/m2, followed by an intravenous (IV) injection of cyclophosphamide four hours later. The cycle was repeated every twenty-one days. The dose of misonidazole remained constant for each regimen, but the dose of cyclophosphamide ranged from 0.4 g/m2 to 1.3 g/m2. Thirty-eight trials in 35 patients with advanced solid tumors were considered evaluable. Dose-limiting toxicity was granulocytopenia at 1 g/m2 of cyclophosphamide without significant thrombocytopenia or anemia. Peripheral neuropathy was negligible. Two patients received cumulative doses of 8 and 16 g/m2 of misonidazole without neurotoxicity. One patient developed hemorrhagic cystitis. Nausea and vomiting was mild to moderate. Possible evidence of tumor stabilization was seen in three patients, and one patient had a mixed response. The mean serum half-life for misonidazole was 11.3 hours (range, 8.4 to 20.0) and for cyclophosphamide 8.3 hours (range, 3.2 to 15.5), both within the previously reported ranges. In conclusion, it appears that this combination is well tolerated and that misonidazole does not significantly potentiate myelotoxicity caused by cyclophosphamide or alter its pharmacokinetics. The recommended starting doses for misonidazole and cyclophosphamide in phase II trials using this schedule of administration should be 2 g/m2 and 1 g/m2, respectively, with escalation for cyclophosphamide to individual tolerance.
Long-term survival in small-cell carcinoma of the lung: a population experience.
Authors: Davis S , Wright P W , Schulman S F , Scholes D , Thorning D , Hammar S
Published: February 2017

Small-cell lung carcinoma (SCLC) is a rapidly progressive and fatal disease. Historically, surgical resection or radiotherapy of the primary tumor has done little to prolong survival, although the use of combination chemotherapy is more effective. Reported here is the survival experience of 1,538 incident cases of SCLC identified through the Surveillance, Epidemiology and End Results Program in western Washington State from 1974 to 1982. The survival experience of this population series is similar to that reported from specialized referral centers. For 71 of 78 persons surviving at least 24 months, the original diagnostic slides were independently reviewed, 47 cases being confirmed as SCLC. No differences were found in actuarial survival estimates between those confirmed and those not confirmed as SCLC. Multivariate survival analysis was conducted to estimate the effects on survival of stage, therapy, age, sex, primary site, and histologic type. All factors except primary site and histologic type significantly influence initial survival rates. However, the only factor related to post--two-year (ie, long-term) survival, once stage is accounted for, is whether surgery was received as a first course of therapy. Those not receiving surgery were at four times the risk of death as those who did. These results indicate that long-term survival can be achieved in patients with SCLC treated in the community, and that the chance of surviving an additional two years for such patients is approximately 40%.
Biliary sclerosis in patients receiving hepatic arterial infusions of floxuridine.
Authors: Hohn D , Melnick J , Stagg R , Altman D , Friedman M , Ignoffo R , Ferrell L , Lewis B
Published: February 2017

High response rates have been reported with hepatic intra-arterial infusions of floxuridine in patients having colorectal carcinoma metastatic to the liver. The major toxicity of this therapy has been described as "chemical hepatitis." In a randomized trial of intravenous v intra-arterial floxuridine, we observed that all 35 patients receiving intra-arterial therapy developed significant increases in alkaline phosphatase and, in some cases, serum glutamic oxaloacetic transminase and/or bilirubin. Seven patients receiving intra-arterial therapy were studied with cholangiography which, in all cases, demonstrated sclerosis of the intrahepatic and/or extrahepatic bile ducts. In addition, liver biopsies showed cholestasis and pericholangitis with minimal hepatocyte damage. These findings suggest that "biliary sclerosis" rather than "chemical hepatitis" is the predominant toxicity associated with hepatic intra-arterial infusions of floxuridine.