Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists' Group.

The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin- or carboplatin-based therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than non-platinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients.

Pericardial angiosarcoma after mediastinal irradiation for seminoma. A case report and a review of the literature.

BACKGROUND: Second malignancies are a well recognized complication of radiation therapy. METHODS: We performed a computer search of the literature using the Medline Database for Pericardial Tumors and Post-Irradiation Sarcomas. RESULTS: The case history of a patient who developed a radiation-induced pericardial angiosarcoma is described. We present a detailed review of pericardial sarcomas. CONCLUSIONS: We believe this to be the first report of a radiation-induced pericardial sarcoma. The importance of continued long-term observation for patients who receive mediastinal irradiation is stressed.

A randomized comparison of cyclophosphamide, Adriamycin, and 5-fluorouracil with triethylenethiophosphoramide and methotrexate, both as sequential and as fixed rotational treatment in patients with advanced ovarian cancer.

The combinations of triethylenethiophosphoramide and methotrexate (TM) and cyclophosphamide, Adriamycin (doxorubicin), and 5-fluorouracil (CAF) were compared, both as sequential and fixed rotational treatments for advanced ovarian cancer, with L-phenylalanine mustard (L-PAM). Treatment with CAF produced a higher response rate (25% complete responses plus 31% partial responses) than treatment with L-PAM (15% complete responses plus 18% partial responses). A fixed rotation of TM and CAF resulted in longer survival (median of 15 months and 75th percentile of 27 months) than sequential treatment with TM initially, followed by CAF upon failure (median of 12 months and 75th percentile of 22 months). The fixed rotation of TM and CAF also increased progression-free survival (median of 12 months and 75th percentile of 24 months) over that achieved by initial treatment with TM (median of 6 months and 75th percentile of 15 months) or L-PAM (median of 9 months and 75th percentile of 21 months). Most patients (96%) on the fixed rotation were treated with both TM and CAF. Fewer patients (62%) on the sequential schedule with TM actually received both combination regimens, and even fewer patients (37%) beginning on CAF ever crossed over to TM. Patient age of 50 years or younger was a favorable prognostic factor for response, survival, and time to first treatment failure (progression-free survival). Disease Stage IIIA or IIIB, surgery including a bilateral salpingo-oophorectomy plus hysterectomy, and treatment within 6 months of initial diagnosis were favorable predictors for both survival and time to first treatment failure. Ambulatory performance status and well-differentiated disease were favorable prognostic factors for survival. Patients with unevaluable disease failed later than those with evaluable disease who, in turn, failed later than patients with measurable disease.

Comparison of melphalan with cyclophosphamide, methotrexate, and 5-fluorouracil in patients with ovarian cancer.

Melphalan (L-PAM) was compared to (C) cyclophosphamide, (M) methotrexate, and (F) 5-fluorouracil (CMF) in 413 patients with advanced ovarian carcinoma. L-PAM was given 3.5 mg/m2 twice daily for 5 days every 5 weeks. CMF doses were: C, 400 mg/m2; M, 15 mg/m2; and F, 400 mg/m2 IV on days 1 and 8 every 28 days. Three hundred seventy-five patients have been analyzed (L-PAM, 190; CMF, 185). One hundred fifty-three patients (41%) had measurable disease, 109 (29%) had evaluable disease, and 113 (30%) had nonmeasurable, nonevaluable disease. Response rates for patients with measurable and evaluable disease combined were similar: L-PAM, 32/130 (24%) (15% complete response); CMF, 47/132 (35%) (18% complete response). Patients with Stage IV measurable disease had a greater response rate to CMF, 22/52 (42%) versus L-PAM, 6/39 (15%). Survival and time to treatment failure were similar for both treatment regimens. Survival was improved in responders. Medians are: complete response, 28.1 months; partial response, 12.3 months; and no response, 6.7 months. Disease stage, performance status and age were identified as important prognostic variables for both survival and time to treatment failure.

Comparative trial of two teniposide-based combination chemotherapy regimens for the treatment of advanced malignant lymphomas.

One hundred and twenty-three patients with advanced measureable malignant lymphomas resistant to conventional chemotherapy were entered in a prospectively randomized trial of two teniposide (VM-26)-based combination chemotherapy regimens: V-PLAT (VM-26, cisplatin, and prednisone) and V-HEX (VM-26, hexamethylmelamine, and prednisone). Ninety-seven eligible and evaluable patients received protocol therapy. Sixteen percent of the patients had Hodgkin's disease, and 84% had non-Hodgkin's lymphoma. All patients were ambulatory (Eastern Cooperative Oncology Group Performance status 0, 1, or 2), 70% had stage IV disease, 59% had "B" symptoms, and all had failed either two or three previous chemotherapy regimens. Toxicity was mainly hematologic and significantly greater with V-PLAT. Objective tumor responses were seen in nine of 45 patients (20%) treated with V-PLAT (duration, 4-35 + weeks) and in four of 51 patients (8%) treated with V-HEX (duration, 10-65 + weeks). Among the 12 patients with histologically confirmed histiocytic lymphoma treated with V-PLAT, five (42%) experienced objective tumor responses, including two complete responses. Overall median survival was approximately 6 months, with no difference between treatment regimens. Limited antitumor activity of these combination regimens in patients with advanced malignant lymphomas has been demonstrated. However, the objective response rates were not higher than we have previously seen with either VM-26 (22%) or hexamethylmelamine (27%) given in maximum tolerable doses as single agents.

Carcinoid tumors of the uterine cervix: response to combination chemotherapy and radiotherapy.

Two cases of advanced (Stage III) carcinoid. tumors of the cervix are presented. Initial treatment in both cases consisted of combination chemotherapy (CCNU, cyclophosphamide and methotrexate) administered in the same regimen used in the treatment of small cell carcinoma of the lung. Initial response in the first case was remarkable, but toxic side effects delayed further treatment. Local tumor progression followed resulting in bilateral complete ureteric obstruction. Radiation therapy was discontinued before an effective dose could be delivered, and the patient expired in uremic coma. In the second case, initial response to chemotherapy was not as effective, but radiation therapy seemed to produce local control of the disease. Review of the English literature produced 21 additional cases of carcinoid tumors of the cervix: eight Stage I, seven Stage II, four Stage III, and one Stage IV. No firm conclusions with regard to therapy could be drawn from such small numbers.

VM-26, a new anticancer drug with effectiveness in malignant lymphoma: an Eastern Cooperative Oncology Group Study (EST 1474).

Thirty-six patients with stage III and IV Hodgkin's disease and non-Hodgkin's lymphoma, who had become refractory to conventional chemotherapy, were treated with VM-26. Complete remissions were documented in two patients with diffuse histiocytic lymphoma. Six patients (four with non-Hodgkin's lymphomas and two with Hodgkin's disease) had partial remissions. The overall response rate was 22% (eight of 36 patients). Hematologic toxicity was the most frequent dose-limiting toxicity. Nonhematologic toxic effects were mild and acceptable. This study demonstrates that VM-26 can produce tumor responses in refractory lymphomas. The Eastern Cooperative Oncology Group is currently planning two new phase II studies to incorporate VM-26 with other active new agents, one involving hexamethylmelamine and the other involving cis-dichlorodiammineplatinum(II).

Doxorubicin hydrochloride-associated renal failure.

Doxorubicin hydrochloride (Adriamycin) therapy was associated with renal failure in a 78-year-old man. The pathophysiologic findings in this patient were similar to those seen following administration of structural analogues of doxorubicin. Daunorubicin hydrochloride, particularly, is known to cause renal failure in experimental animals. Renal function should be monitored in patients receiving doxorubicin.

Cyclophosphamide and CCNU in the treatment of inoperable small cell carcinoma and adenocarcinoma of the lung.

Two hundred and fifty-eight patients with small cell carcinoma and 185 patients with adenocarcinoma were centrally randomized to receive either cyclophosphamide (1000 mg/m2 every 3 weeks) iv or cyclophosphamide (700 mg/m2 every 3 weeks) iv plus CCNU (70 mg/m2 every 6 weeks) orally. Those patients who were initially treated with the single agent were then treated with CCNU (130 mg/m2 every 6 weeks) at the time of cyclophosphamide failure. Objective tumor regression occurred more frequently with the combination regimen in patients with small cell carcinoma (43% vs 22%, P = 0.002), but no difference in response rates was apparent in patients with adenocarcinoma. In both cell types patients survived somewhat longer following treatment with the combination. The overall incidence of severe toxicity was equal for the two regimens in both cell types; however, the therapeutic index of the combination was superior to that of the single agent in small cell carcinoma. Severe drug toxicity was more frequent in small cell carcinoma patients with extensive disease, and survival was reduced in both cell types with extensive disease. Survival was better for ambulatory patients in both cell types and women survived longer than men. In women with small cell carcinoma, ambulatory status also was associated with a higher incidence of tumor regression. In patients with small cell carcinoma those who had prior lung surgery survived longer than those without prior surgery. Previous radiation therapy was associated with a reduced incidence of objective regression in men with small cell carcinoma. In both cell types patients with tumor regression lived longer than nonresponders; however, objective disease stability was associated with improved survival only in patients with adenocarcinoma. Stratification in future studies should consider extent of disease, performance status, sex, and prior therapy.