Fraile Rj

VM26 (NSC-122819): A clinical study in advanced cancer of the lung and ovary☆

Abstract Fifty-five evaluable patients with advanced carcinoma of the lung ( 25 squamous, 19 adeno, 11 small cell) and 16 patients with advanced adenocarcinoma of the ovary were treated with VM 26 in a phase II study. Only one response was noted, a partial (> 50% ) remission in squamous cell cancer of the lung for 8 + months. The drug was well tolerated with minimal nausea, vomiting, anorexia and alopecia. Myelosuppression was infrequent in patients not previously treated with chemotherapy and usually tolerable in patients previously treated. Orthostatic hypotension, hepatotoxicity and peripheral neuropathy were not observed. On the basis of this report VM 26 does not appear to demonstrate any significant antitumor effect in advanced cancer of the lung and ovary.

A phase i‐ii study of maytansine utilizing a weekly schedule

Maytansine, a new ansa macrolide antitumor antibiotic, was administered to a total of 107 patients in a Phase I‐II study. Dose‐limiting toxic reactions which occurred at 0.75–1.0 mg/M2 in both Phase I and II were neurologic and consisted primarily of lethargy/weakness (a debilitation syndrome) and paresthesias. Gastrointestinal and neurologic toxic reactions increased in frequency and severity as a function of dose. Myelosuppression, while infrequent, occurred only in previously treated patients. Changes in liver function tests were subclinical. Two partial remissions were observed at a dose‐level of 0.5 mg/M2 in Phase I: 1 patient with squamous cell carcinoma of the lung responded for five weeks, while the other patient with adenocarcinoma of the lung responded for four weeks. One partial remission, lasting 14 weeks was seen in Phase II in a patient with malignant melanoma treated at a dose‐level of 1.0 mg/M2. All responses were in heavily pretreated patients. Pairs of small bowel biopsy specimen used to define the mitotic index demonstrated peak mitotic arrest at 24 hours in contrast to vinca alkaloids which appear to have a peak mitotic arrest at 12–24 hours.

Phase II evaluation of chlorozotocin (NSC-178248) in advanced human cancer

Abstract A phase II evaluation of chlorozoticin (CZT), a water soluble nitrosourea, was undertaken to determine its effectiveness and toxicity in a variety of human metastatic neoplasms. The dosage regimen chosen was either 90 or 120 mg/m 2 given by i.v. bolus every six weeks. Dosage escalation or de-escalation was dependent on toxicity. There have been 152 patients evaluable for response. The only significant response rates observed were in non-Hodgkins lymphoma ( 5/11 ) and sarcoma ( 4/27 ). Single responses were observed in breast and oat cell carcinoma of lung. No responses were observed in melanoma, colorectal, kidney, non-oat cell lung, pancreas, stomach and other carcinomas. Hematological toxicity has been minimal as predicted, but does appear to be cumulative. The major G.I. toxicity has been nausea and vomiting—usually controllable. Occasional hepatic enzyme elevations were observed, and azotemia was observed in 6 patients. Both were reversible. Rare skin and occasional CNS reactions were also seen.

Combination chemotherapy with mitomycin C, adriamycin, and cyclophosphamide (MAC) in stage III and IV ovarian cancer

Twenty-nine patients with stages III and IV epithelial carcinomas of the ovary were treated with a combination of mitomycin-C, adriamycin, and cyclophosphamide (MAC). A 62% response rate (CR + PR) was observed in previously untreated patients with a median survival of responding patients of 100+ weeks, compared to 29 weeks for nonresponding patients (p less than 0.001). Toxicity was acceptable with moderate to severe but manageable myelosuppression. Prospective, randomized trials comparing this drug combination to others with demonstrated efficacy are indicated.