Showing papers on "Phases of clinical research published in 1977"

Phase II study of 5-azacytidine in solid tumors.

Abstract: One hundred and seventy-seven patients were evaluated after therapy with 5-azacytidine using a dose of 1.6 mg/kg/day X 10 days followed by a maintenance regimen. One hundred and forty-eight of the patients received the drug by rapid iv infusion and 29 received the drug daily by and infusion that lasted between 18 and 24 hours. Hematologic toxicity was significant but transient in both groups. Nausea was severe using the rapid iv infusion and minimal with the slow infusion. Antitumor effect was seen in 17% of the evaluable patients with carcinoma of the breast and 21% of the patients with malignant lymphomas. Occasional responses were seen with a variety of other solid tumors. The responses were transient, and clinically, resistance to 5-azacytidine appeared to develop quite rapidly. No clear-cut difference was seen in response rates or duration of response between the two groups of patients. Cross resistance to other anticancer agents was not noted. It is believed that the drug is only of minimal value as a single agent in solid tumors using either of the methods of administration described.

Treatment of small cell anaplastic carcinoma of the lung with the oral solution of VP‐16‐213 (NSC 141540, 4′‐demethylepipodophyllotoxin 9‐(4,6‐0‐ethylidene‐β‐D‐glucopyranoside)

Abstract: The semisynthetic podophyllotoxin derivative VP-16-213 (NSC 141540) has been evaluated in a phase II study in patients with small cell anaplastic carcinoma of the lung. The drug was administered as an oral solution, the drinking ampoule, in doses of 100 mg twice a day for 4 days in 30 patients previously treated with intensive combination chemotherapy and for 5 days in 10 untreated patients. The courses were repeated every third week with dose modifications according to individual tolerance. All patients had measurable disease and objective responses were obtained in 20 patients (50%), 15 previously treated (50%) and 5 untreated patients (50%). The median time for response after the start of treatment was 15 days (range 6–42) and the median duration of response was 56 days (range 16–147). Dose-limiting toxicity was principally hematologic, consisting of leukopenia, but gastrointestinal toxicity and alopecia were also observed. The study demonstrated that VP-16-213 administered as an oral solution is highly effective against small cell anaplastic carcinoma of the lung without clinical cross-resistance to CCNU, cyclophosphamide, methotrexate, or vincristine. Cancer 40:633–637, 1977.

Phase II study of 5-azacytidine in solid tumors.

Abstract: A phase II study utilizing 5-azacytidine in the treatment of patients with solid tumors was carried out by the Southwest Oncology Group (SWOG-7208). Of 214 patients entered in the study 191 were eligible and 167 were evaluable. While initially they received 225 mg/m2 iv on Days 1--5 every 3 weeks because of toxicity the dose was subsequently reduced to 175mg/m2 and later to 150 mg/m2. Five partial regressions, 2.6% of the eligible patients and 3% of the evaluable patients, lasting from 28 to 77 days were observed. Sixteen patients 8.4% of the eligible patients and 9.6% of the evaluable patients, had no significant change in their disease for 39--255 days. The major toxicities were myelosuppressive and gastrointestinal with 13 deaths attributable to drug toxicity: 11 due to sepsis and two due to cerebral hemorrhage. 5-Azacytidine induced few favorable responses; those that did occur usually were of poor quality and short duration and were associated with significant toxicity.

Twice weekly 5-azacytidine infusion in dissmeinated metastatic cancer: a phase II study.

Abstract: A phase II study of 5-azacytidine given twice weekly as a rapid iv infusion was performed on 116 patients with different metastatic cancers of refractory lymphomas at a dose of 150 mg/m2 twice weekly x 6 Ninety-one patients were evaluable Dose modifications were carried out depending on previous treatment status Nausea and vomiting was a major side effect; significant granulocytopenia was observed in 35 patients Responses were observed in only four patients Our results indicate little effectiveness of this drug The severe toxicity prevented escalation to potentially more effective dose levels

Phase II study of oral methyl-CCNU and prednisone in previously treated alkylating agent-resistant multiple myeloma.

Abstract: Thirteen patients with multiple myeloma (MM) who either failed to respond to or who were relapsing from standard agents and who received four or more courses of methyl-CCNU + prednisone (adequate drug trial) are reported in this paper. Methyl-CCNU was given orally before breakfast at 6-week intervals at a starting dose of 50 mg/m2 with the intention of increasing the dose to 100, 150, and 200 mg/m2 with each subsequent course. The dose of prednisone was 75 mg/day x 7 with each course. The response rate was 46% (six of 13 patients). No patient had better than a fair response. Drug toxicity, severe enough to prevent further dose escalation, was observed in every case. Prior BCNU therapy or the lack of response to previous alkylating agents did not prevent a response to methyl-CCNU + prednisone. The response rate of methyl-CCNU + prednisone in MM is comparable to the results achieved with other agents in similar groups of patients.