Sandra J. Ginsberg

A randomized comparison of methotrexate dose and the addition of bleomycin to chop therapy for diffuse large cell lymphoma and other non-Hodgkin's lymphomas cancer and leukemia group B study 7851

In 1978, Cancer and Leukemia Group B initiated a randomized study to determine the usefulness of the addition of bleomycin and/or high‐dose methotrexate to standard therapy for the treatment of certain adult non‐Hodgkins lymphomas. Between 1978 and 1985, 177 patients with diffuse large cell lymphoma (DLCL) and 97 patients with other intermediate‐grade non‐Hodgkins lymphoma were randomized to receive therapy with three courses of cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) every 3 weeks with or without low‐dose bleomycin by continuous IV infusion. Responders after three courses were further randomized to 3 weeks of therapy with either high‐dose methotrexate (3 gm/m2/week intravenously with leucovorin rescue) or standard‐dose methotrexate (30 mg/m2/week orally without rescue). Therapy was concluded with three additional courses of CHOP. Neither the addition of low‐dose infusion bleomycin nor the use of high‐dose rather than low‐dose methotrexate had significant effects on response for patients with DLCL; complete response rates for the four treatment programs ranged from 47% to 51%. Median failure‐free survival (FFS) for the entire group of DLCL patients was 12 months; 5‐year FFS was 27%. There was no significant effect on FFS from the addition of either low‐dose bleomycin to CHOP (5‐year FFS: CHOP, 28%; CHOP‐B, 26%, P = 0.81), or from the use of different doses of methotrexate (5‐year FFS: high‐dose, 34%; standard‐dose, 33%, P = 0.51). Patients with follicular large cell lymphoma, with or without diffuse areas, had a better FFS (5‐year FFS, 47%) than patients with DLCL (5‐year FFS, 27%), while the patients with the other histopathologic subtypes of diffuse lymphomas had the poorest FFS (5‐year FFS, 16%).

A phase II trial of iproplatin (CHIP) in previously treated advanced breast cancer

Iproplatin (CHIP) was administered to 35 previously treated women with metastatic adenocarcinoma of the breast. The drug was given at a dose of 45 mg/m2 intravenously for 5 consecutive days and was repeated every 28 days. In this trial, there was one partial response and two patients with stable disease out of 29 evaluable patients. The median duration of response in patients with either a partial response or stable disease was 4.8 months. Myelosuppression was the major toxicity, 11 patients had severe thrombocytopenia and 3 severe neutropenia. Mild renal insufficiency, anemia, and nausea and vomiting were also noted. Iproplatin has limited activity in heavily pretreated women with advanced breast carcinoma; further studies in patients less heavily treated may show an improved response rate.

Combination Chemotherapy and Radiotherapy in Smalt-Cell Carcinoma of the Lung

A combination of chemotherapy (Cytoxan, vincristine, and CCNU) and radiation therapy was used to treat 37 patients with small-cell carcinoma of the lung. There was 49% complete remission and an overall 76% objective response with an overall median survival of 12.5 months and 17 months for those showing a complete response. No serious morbidity was observed.

Phase Ii Study of Iproplatin (chip) in Previously Treated Small-cell Lung Cancer

Eighteen patients with previously treated extensive small-cell carcinoma of the lung were entered into a Phase II study employing iproplatin (CHIP), a cis-platin analog. Patients had received a mean of two prior chemotherapeutic regimens. Fifty-five percent had received prior cis-platinum and 33% had received prior radiation therapy. CHIP (225 mg/m2) was administered by intermittent intravenous infusion over 30 min for 5 days of a 28-day cycle without prehydration. Sixteen patients with Zubrod performance scores of <3 received 27 courses of therapy (mean 1.7, range 1–6). One partial response of 167 days duration was observed, with complete regression of involved lymph nodes and stabilization of nonevaluable disease in the chest. Six patients had stable disease following one cycle of CHIP, but all progressed following a second cycle of drug. The main toxicity was myelosuppression with prominent thrombocytopenia. Median survival was 75 days from initiation of therapy. In this group of heavily pretreated patients with advanced disease, iproplatin has only minimal activity as a single agent and does not show non-cross-resistance with cis-platinum.

Phase II trial of iproplatin (CHIP) in previously untreated patients with colorectal cancer

Nineteen previously untreated patients with colorectal cancer and measurable disease were treated with iproplatin (CHIP), 75 mg/m2 daily, for 5 days every 4 weeks for at least 2 courses. Toxicities included myelosuppression, mild nausea and vomiting, and rare mild nephrotoxicity. The dose-limiting toxicity was thrombocytopenia, which appeared to be cumulative. Dose reduction was frequently necessary. There were no toxic deaths. One partial response was observed, and four patients had stable disease for a median of 2 months. Iproplatin does not appear to have significant activity against colorectal cancer.