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Biomedical subjects

G Falkson

Publications and source records attributed to G Falkson.

At least 199 records · Page 11Linked to original sources

Fluorouracil, imidazole carboxamide dimethyl triazeno, vincristine, and bis-chloroethyl nitrosourea (FIVB) in colon cancer.

One hundred and sixty patients with advanced metastatic colon cancer were treated with the drug combination of 5-fluorouracil (FU), imidazole carboxamide dimethyl triazeno (ICDT, DTIC), vincristine (VCR), and bis-chloroethyl nitrosourea (BCNU). All the agents were given in each cycle of treatment. The patients also received continuous ethylestranol. Special care was taken to ensure that the ICDT was not at any time exposed to light. Toxic effects included fall in hemoglobin, leukopenia, thrombocytopenia, alopecia, stomatitis, nausea and vomiting, and occasional diarrhea. Among 112 patients who had had no prior exposure to cytostatic agents, complete remission (CR) was recorded in 12, and partial remission (PR) in 31. The median duration of remission in these patients was 5.2 months. The median survival for the whole group was 8.4 months: for responders the median survival was 10 months, and for non-responders, 5.4 months. PR was also documented in 10 of 48 patients who had received prior treatment with FU or FU plus methyl-1,3-cis(2-chloroethyl-1-nitrosourea) (MeCCNU).

Antineoplastic Agents↗

A phase II study of m-AMSA in patients with primary liver cancer.

Thirty-five evaluable patients with histologically confirmed primary liver cancer (PLC) were treated with m-AMSA. All patients had measurable disease and an Eastern Cooperative Oncology Group (ECOG) performance status of 1, 2, or 3. m-AMSA 120 mg/M2 IV was given every 21 days. Hemopoietic suppression was the major side-effect. In 26 of 35 patients (25 with leukopenia and five with thrombocytopenia), this toxic effect was documented. There was only one patient who had a partial remission (PR) of 51 weeks' duration, but a no change (NC) status was maintained in 28 patients for at least 6 weeks. The median survival time of all patients on this study was 13 weeks, which compares favorably with most previous studies.

Adult↗

A prospective evaluation of chemohormonal therapy remission maintenance in advanced breast cancer.

From October 1973 to October 1977 the ECOG prospectively evaluated cyclophosphamide, methotrexate, and fluorouracil (CMF) versus CMF plus fluoxymesterone (CMFH) maintenance therapies in responders to 6 months of induction therapy which consisted of either CMF, CMF plus prednisone (CMFP), or adriamycin plus vincristine (AV). Following the maintenance randomization 12% of the patients converted from a PR to a CR status. The median time from randomization to treatment failure was 9.5 months for CMFH and 6.7 months for CMF (p = 0.03). This difference was observed only for partial responders (p = 0.01) and not for complete responders. Patients receiving CMFH tended to maintain higher hemoglobin, leukocyte, and platelet levels, and receive a higher dosage of each of the cytotoxic drugs. The results are taken as evidence that the addition of fluoxymesterone to a maintenance CMF regimen provides a therapeutic advantage. It is hypothesized that this effect is due at least in part to fluoxymesterone associated maintenance of improved marrow function resulting in greater myelosuppressive drug delivery.

Aged↗

Phase I--II evaluation of combination cyclophosphamide, 5-fluorouracil, hexamethylmelamine, and prednisone in advanced breast cancer.

A four-drug combination of intermittent high-dose cyclophosphamide with 5-fluorouracil, hexamethylmelamine, and prednisone was given to 19 patients with advanced breast cancer. Objective response was documented in 7 of 18 evaluable patients. The median duration of response was 99 days. Response was observed in 6/7 patients without visceral disease and 1/11 patients with visceral disease. Toxicity was acceptable and no life-threatening toxicity was observed. Three patients have received the four-drug combination for more than 1 year without serious side effects. This regimen may serve as an alternative treatment for patients without visceral metastasis who have failed to respond to other combination chemotherapy regimens.

Adenocarcinoma↗

A five-drug combination in the treatment of metastatic breast cancer.

The five-drug combination of fluorouracil imidazole carboxamide dimethyl triazeno, vincristine, bis-chloroethyl nitrosourea, and prednisone (FIVB + P) was given to 120 women with metastatic breast cancer. Of 114 evaluable patients, complete response was seen in 12 and partial remission in 39. Complete or partial remission was documented a) in 21 of 59 patients who had had extensive prior chemotherapy and prednisone, b) in 15 of 33 patients who had had prior chemotherapy but no prior prednisone, and c) in 15 of 22 patients who had received no prior systemic treatment for breast cancer. The regimen was well tolerated, the main side effects being hemopoietic suppression, short duration nausea and vomiting, and alopecia. The FIVB + P regimen is a useful and acceptable second or third line treatment for patients with metastatic breast cancer. There is evidence that this treatment program provides a non-cross-resistant regimen to many chemotherapy combinations currently in use in breast cancer. The high activity in previously untreated patients offers a further option for cycling of multiple agents in order to gain better disease control in patients with advanced breast cancer.

Antineoplastic Agents↗

Vindesine. A phase II trial in advanced breast cancer patients.

A phase II trial of vindesine (VDS), a new vinca alkaloid, has been carried out in 40 patients with metastatic breast cancer. Patients entered in the study had been previously treated with an average of two chemotherapy regimens. Treatment was given as a weekly I.V. bolus of VDS at 3 mg/m2. The response rate in 31 evaluable patients was 19%, i.e., one complete response (CR), four partial responses, and one improvement in osseous disease (IMP). In 36 patients evaluable for toxicity, neurological and hematological toxicity was most significant. Half the patients treated had received previous vincristine therapy; this factor did not appear significant with regard to toxicity or response to VDS.

Adult↗

Chemotherapy of advanced esophageal carcinoma: Eastern Cooperative Oncology Group experience.

In a Phase II study, patients with measurable metastatic or recurrent esophageal carcinoma randomly received after Adriamycin (ADR), 60 mg/M2 I.V. q three weeks, or methotrexate (MTX), 40 mg/M2 I.V. q one week, or 5-fluorouracil (5-FU), 500 mg/m2 I.V. x 5 days q five weeks. Objective partial response rates for 72 patients were 5% for ADR (one of 20), 12% for MTX (three of 26), and 15% for 5-FU (four of 26). There were no complete responses. Median duration of response was 13 weeks. Median survival was 14 weeks (eight weeks for ADR, 14 weeks for MTX, and 15 weeks for 5-FU). Factors of liver metastasis, adjacent anatomic involvement, time from initial diagnosis to study entry, and prior radiation were found to be significant determinants of survival. Adriamycin did not appear to benefit patients with advanced measurable squamous cell carcinoma of the esophagus. Methotrexate and 5-fluorouracil showed comparable activity and survival, although methotrexate was slightly more toxic.

Antineoplastic Agents↗

A new effective four-drug combination of CCNU (1-[2-chloroethyl]-3-cyclohexyl-1-nitrosourea) (NSC-79038), vinblastine, prednisone, and procarbazine for the treatment of advanced Hodgkin's disease.

Five hundred and sixty-six patients with either Stage III or IV Hodgkin's disease were prospectively randomized to test whether CCNU and/or vinblastine are more effective than mechlorethamine and/or vincristine with procarbazine and prednisone. The combination of CCNU, vinblastine, procarbazine, and prednisone (CVPP) was shown to be a highly effective program with a complete response frequency of 69%. The use of CCNU as part of the induction program was also shown to be the most significant determinant of prolonged remissions (P = .025). Reduced vomiting and neurotoxicity, as well as the oral administration, were the chief advantages of the CVPP as compared with MOPP. These factors resulted in improved patient and physician compliance. The MVPP regimen was also shown to be a highly effective regimen with a complete response frequency of 73% in patients without prior exposure to chemotherapy. However, the induction regimens containing vinblastine were associated with a significantly higher frequency of fatal hematopoietic toxicities than the induction regimens containing vincristine (P = .05). This higher frequency was almost exclusively seen in the elderly or in patients previously treated with both chemotherapy and radiotherapy. At this time, the remission durations maintained by vinblastine with periodic reinforcement are longer when compared with vinblastine maintenance alone (P = .06), but there is no corresponding increase in survival.

Adult↗

Non-Hodgkin's lymphoma in pregnancy.

Non-Hodgkin's lymphoma associated with pregnancy is rare. To date, only 1 case in which lymphoma was diagnosed and treated during pregnancy, with normal pregnancy outcome, has been reported. We describe another case where life-threatening, diffuse, poorly differentiated lymphocytic lymphoma was diagnosed during the 13th week of pregnancy. Combination chemotherapy (cyclophosphamide, vincristine, bleomycin, and prednisone) resulted in remission and a health full-term infant was born.

Adult↗

Clinical trial of VP 16--213 (NSC 141540) I.V. twice weekly in advanced neoplastic disease: a study by the Cancer and Leukemia Group B.

The epipodophyllotoxin derivative VP 16--213 (NSC 141540) was studied by the Cancer and Leukemia Group B in a broad phase II trial at three dose levels: 60 mg/m2, 90 mg/m2, and 135 mg/m2 I.V. twice weekly. No correlation between dose of VP 16--213 and response frequency in a particular disease category could be demonstrated. Of the 382 patients, 8% obtained a complete (CR) or partial remission (PR), 8% showed improvement, and 14% had stable disease. By tumor type the best responses were obtained in lymphomas (8/31 CR + PR), uterus (2/9), prostate (1/5), rhabdomyosarcoma (2/6), neuroblastoma (2/4), colon/rectum (5/81), other gastrointestinal (4/32). In lung tumors, 4/80 patients obtained CR or PR. VP 16--213 has definite antineoplastic activity but the response frequency with the twice weekly schedule may be lower than that reported with other schedules.

Adult↗

A phase II study of neocarzinostatin (NSC 157365) in malignant hepatoma. An Eastern Cooperative Oncology Group pilot study.

Thirty evaluable patients with histologically confirmed primary liver cancer (PLC) were treated with neocarzinostatin (NCS). All patients had measurable disease and an Eastern Cooperative Oncology Group (ECOG) performance status of 1, 2, or 3. NCS 2250 units/m2 was given daily for 5 days, repeated at 28-day intervals. Hemopoietic suppression was the major side effect. In 23 of 30 patients (13 with leukopenia and 19 with thrombocytopenia), this toxic effect was documented. Other toxic effects included nausea, vomiting, allergic-type reaction, and elevation of NPN. Partial response, with a median duration of 12.7 weeks (range 4--37 weeks) was observed in seven patients. In nine patients the response was classified as no change, and in 14 patients there was progressive disease. NCS has some therapeutic activity in patients with PLC.

Adult↗

Anhydro-ara-5-fluorocytidine (AAFC) in gastrointestinal cancer. A phase II study.

Results of a phase II study of AAFC in 32 patients with advanced measurable gastrointestinal cancer are presented. Fourteen patients were treated with a weekly schedule, while 18 were treated with 5-day courses of the drug. There were 12 patients with pancreas cancer, eight with stomach cancer, seven with cancer of the esophagus, four with colorectal cancer, and one with cancer of the gallbladder. Response was observed in pancreas and stomach cancer. Two patients with pancreas cancer had partial remissions, three other patients (two pancreas and one stomach) had response of short duration, considered to be less than a partial remission. There appeared to be very little difference between the two different schedules of administration. AAFC shows limited activity in adenocarcinoma of pancreas and stomach; there does not appear to be a practical application for AAFC as a single agent.

Ancitabine↗

A comparative study of a BCNU containing 4-drug program versus MOPP versus 3-drug combinations in advanced Hodgkin's disease: a cooperative study by the Cancer and Leukemia Group B.

A prospective randomized trial by CALGB examined the relative value of four chemotherapy regimens in 537 patients with stage III B and IV Hodgkin's disease. A new combination BOPP, derived by substitution of BCNU for nitrogen mustard in the MOPP regimen, was compared to MOPP and to two 3-drug regimens, derived by removing the procarbazine in BOPP (BOP) or removing the alkylating agent (OPP). The 4-drug programs gave significantly higher frequency of complete remissions (BOPP 67%, MOPP 63%) than the 3-drug regimens (BOP 40%, OPP 42%), and significantly longer duration of remission and survival. BOPP had a therapeutic activity equal to MOPP, and was accompanied by less toxicity. After 6 cycles of induction chemotherapy, responding patients, both CR and PR, were continued on maintenance chemotherapy for 3 years. No significant difference in relapse rate was demonstrated following maintenance treatment with either vinblastine, chlorambucil, or chlorambucil plus monthly vincristine + prednisone doses. Nor could a reinforcement phase late in the maintenance program be shown to influence the relapse rate. The median survival for all patients entered on the 4-drug programs was 5 years, while the median has not yet been reached at 6 years for those patients, who obtained CR.

Adult↗

Improved remission rates and remission duration in young women with metastatic breast cancer following combined oophorectomy and chemotherapy: a study of Cancer and Leukemia Groupe B.

One hundred fifty-seven premenopausal women with metastatic breast cancer were prospectively randomized to treatment consisting of oophorectomy + vincristine, prednisone, cyclophosphamide, methotrexate, 5-fluorouracil (VPCMF) (Reg. I) or oophorectomy + cyclophosphamide (Reg. II) or oophorectomy followed by an observation period (Phase 1), followed by VPCMF (Phase 2) (Reg. III). Complete plus partial response rates were 72% on Reg. I, 65% on Reg. II, 18% on Reg. III, Phase 1 and 50% on Reg. III, Phase 2. Median duration of response for Reg. I was 17 months, for Reg. II 16 months, and for Phase 1 and Phase 2 of Reg. III, respectively, 5 months and 8 months. The response rate for patients treated with oophorectomy plus chemotherapy is significantly higher than the response rate achieved with oophorectomy alone as first treatment following the appearance of metastases in premenopausal women.

Adult↗

Combination chemotherapy for non-Hodgkin lymphomas: a ten year follow-up study.

In 1968 the Cancer and Acute Leukemia Group B (CALGB) demonstrated optimal control of disseminated non-Hodgkin lymphomas (NHL) with vincristine-prednisone induction followed by cyclophosphamide maintenance. A study was then begun to determine whether four drugs in combination or sequence could achieve greater control. NHL patients at each participating CALGB institution were randomly assigned to one of three regimens:I) Cyclic vincristine-streptonigrin alternating every 2 weeks with cyclophosphamide-prednisone up to 155 days; II) Sequential treatment with the same 4 drugs taken singly up to 182 days; and III) Vincristine-prednisone induction for 6 weeks followed by cyclophosphamide maintenance. Results are now reported after a 10 year follow-up period. The 203 evaluable patients are those on whom Rappaport histopathologic classification was available. Frequency of complete-response did not differ significantly among the three regimens: I) 38%; II) 30%; and III) 45%. Remission durations were significantly longer among patients receiving maintenance therapy. After ten years, two patients from Regimen I, one from Regimen II, and five from Regimen III remain alive and well. It was concluded that neither of the four-drug regimens conferred a significant advantage in terms of response rate or survival time over the standard treatment.

Antineoplastic Agents↗