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PubMedDate not supplied

Treatment of small cell carcinoma of the lung using methyl-CCNU (NSC-95441) combined with cyclophosphamide (NSC-26271) and vincristine (NSC-67574) in a 3-week schedule.

Twenty-six patients with small cell carcinoma of the lung were treated with a combination of methyl-CCNU (75 mg/m2 orally), cyclophosphamide (750 mg/m2iv), and vincristine (1.4 mg/m2iv) once every 3 weeks and followed for 2-56 weeks (mean, 24 weeks). An average of seven treatments were given per patient. Myelotoxicity was mild to moderate with no white blood cell count (wbc) less than 1000 cells/mm3 and no platelet count less than 25,000 cells/mm3. Six patients (23%) had a wbc of 1000-2000 cells/mm3 and two (8%) had a platelet count of 25,000-75,000 cells/mm3. Sixty-eight persons of the projected dose of methyl-CCNU was given. Fourteen of 22 patients with measurable disease (54%) responded. Of 14 patients who had received no prior treatment 64% responded with a median survival duration of 40 weeks. Complete responses occurred only in patients without prior radiation therapy or chemotherapy. We conclude that methyl-CCNU may be given with an acceptable level of toxicity in an every 3-week schedule and that the combination of cyclophosphamide, methyl-CCNU, and vincristine warrants further evaluation in the treatment of small cell carcinoma of the lung.

Adult↗
PubMed1976

Nitrosoureas: a review of experimental antitumor activity.

The chemical class of drugs known as the nitrosoureas are a recently developed group of very active alkylating-agent anticancer drugs which are best represented by BCNU, CCNU, and methyl-CCNU (meCCNU). The nitrosoureas are among the most active, if not the most active, anticancer drugs both quantitatively (log kill of sensitive tumor cells in vivo) and qualitatively (spectrum of mouse, rat, and hamster tumors responding to treatment). Therapeutic anticancer activity of the nitrosoureas has been consistently observed with oral as well as parenteral administration. The nitrosoureas are clearly the most active group of anticancer drugs observed against experimental meningeal leukemias and intracerebrally implanted transplantable primary tumors of central nervous system origin (eg, gliomas, ependymoblastomas, and astrocytomas in mice and hamsters). The nitrosoureas have been observed to be less than additive in lethal toxicity for vital normal cells in the mouse in combination with representatives of the other major classes of anticancer agents, eg, purine antagonists, pyrimidine antagonists, inhibitors of DNA polymerase(s) or ribonucleotide reductase(s), mitotic inhibitors, drugs that bind to or intercalate with DNA, and other alkylating agents. Therapeutic synergism against one or more transplantable or spontaneous tumors of mice, rats, or hamsters with one of several nitrosoureas in two-drug combinations with representatives of most of the major classes of anticancer agents listed above has been reported. With a number of advanced-stages mouse tumors, generally considered to be refractory to treatment with most anticancer agents, long-term cures have been obtained with combination-drug or combined-modality (surgery plus chemotherapy) treatment. The demonstrated lack of cross-resistance of several leukemias and solid tumors of mice selected for resistance to BCNU, meCCNU, or other alkylating agents suggests that the widely held opinion that all alkylating agents are very similar in biologic mechanism of action, and therefore resistance to one alkylating agent probably predicts cross-resistance to all alkylating agents, may no longer be tenable. If not, then alkylating-agent drug combinations, either used alone or combined with other treatment modalities (eg, surgery) which have been reported to result in therapeutic improvement in a number of experimental murine tumor systems, may be indicated for serious consideration as surgical adjuvant chemotherapy by surgeons or as primary therapy by medical oncologists.

Animals↗
PubMed1976

Nitrosoureas in the management of disseminated malignant melanoma.

Three of the nitrosoureas, BCNU, CCNU, and methyl-CCNU, have displayed significant antitumor activity in patients with disseminated malignant melanoma with none clearly superior to the others, although direct comparison in clinical trials was not accomplished. Response rates to various combinations of these nitrosoureas seem a bit higher, but not dramatically so, when compared to the single-agent response rates, although again this cannot be stated with certainty since direct comparisons were not accomplished. There appears to be no therapeutic advantage to the utilization of any one of the nitrosoureas over the others, but oral administration, as is available for CCNU and methyl-CCNU, is a distinct advantage to the patient and to the clinician. The response rates are, for the most part, rather consistent for the various studies reported in this paper, and these response rates leave a great deal of room for improvement. Secondary therapy utilizing the nitrosoureas was singularly unsuccessful in most of the reported clinical trials. It is refreshing, however, to have agents which have shown activity, although modest, in this most refractory of neoplasms.

Carmustine↗
PubMed1976

Nitrosoureas: useful agents for the treatment of advanced gastrointestinal cancer.

Patients with a wide range of gastrointestinal cancers have been treated with nitrosoureas by the Eastern Cooperative Oncology Group. Methyl-CCNU, CCNU, and streptozotocin have been evaluated as single agents in the treatment of colorectal carcinoma. Methyl-CCNU has had an extensive trial in gastric carcinoma as a single agent and in combination with 5-fluorouracil (5-FU). It has also been used to treat pancreatic carcinoma and, in a few patients, carcinoma of the biliary tract. In gastric cancer it would appear that a synergistic effect on response rates has resulted from the combination of methyl-CCNU and 5-FU. The addition of cyclophosphamide to this combination as an induction agent detracted significantly.

Clinical Trials as Topic↗
PubMed1976

Southeastern Cancer Study Group trials with nitrosoureas in Hodgkin's disease.

A decade of studies with the nitrosoureas in the Southeastern Cancer Study Group has shown that they are active agents for the treatment of Hodgkin's disease and that they may be combined with other chemotherapeutic agents in regimens which have acceptable toxicity to produce excellent response rates. Further more, six monthly cycles of treatment with a combination of either BCNU, vinblastine, cyclophosphamide, procarbazine, and prednisone or mechlorethamine, vincristine, prednisone and procarbazine(MOPP), following the achievement of a clinical CR, produce significantly superior durations of remission and survival in previously untreated patients. Our studies with BCNU given orally have indicated that it is not a clinically useful drug. Finally, studies with methyl-CCNU given orally have indicated no particular place for this agent in the treatment od Hodgkin's disease when compared to CCNU and BCNU.

Administration, Oral↗
PubMed1994

Adjuvant postoperative therapy of gastrointestinal malignancies.

Postoperative treatment with adjuvant chemotherapy with or without radiation has been extensively studied in cancers of the gastrointestinal tract. Clinical trials of adjuvant postoperative chemotherapy in gastric cancer have failed to show a survival benefit, and although studies in pancreatic cancer suggest a benefit for postoperative concurrent chemoradiotherapy, confirmatory trials have not been performed. In contrast, adjuvant therapy for cancers of the colon and rectum has been shown to improve survival in patients at significant risk for disease recurrence. For Dukes' C colon cancer, postoperative adjuvant chemotherapy with a combination of fluorouracil and levamisole is now recommended as standard therapy. Recent studies suggest that adjuvant therapy with fluorouracil plus leucovorin also improves disease-free survival; longer follow-up is needed to assess effects on overall survival. For Dukes' B2 and C rectal cancer, standard therapy is postoperative treatment with fluorouracil-based chemotherapy and concurrent pelvic radiotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1977

Chemotherapy of an experimental glioma with nitrosoureas.

Chemotherapy experiments were performed with 2 nitro-sourea drugs in an experimental mouse brain tumor model. Cell suspensions of a transplantable mouse ependymoblastoma were injected i.c. by means of a stereotactic frame. The drugs used were 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea and were given by either i.p. or by direct intraneoplastic (i.n.) injection on the fifth day after tumor cell implantation. Injections i.n. of drugs were made with the stereotactic frame. Both drugs were highly effective in increasing the median day of death and in yielding large numbers of long-term survivors. Effectiveness was evident after i.p. or i.n. injection. However, with certain dosage schedules such as every 2 hr for 5 injections daily on 2 consecutive days, i.n. injection was more effective and less toxic than i.p. injection. The reason why repeated i.n. injections produced less toxicity than repeated i.p. injections is not definitely known but may be due to local metabolism of the drugs in the tumors and surrounding brain to a less toxic form. This is the first laboratory report of direct i.n. injection of the nitrosoureas, and the authors consider these results encouraging.

Animals↗