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Results for “Semustine”

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At least 19 recordsLinked to original sources

PubMed1981

Nephrotoxicity of semustine (methyl-CCNU) in patients with malignant melanoma receiving adjuvant chemotherapy.

The nephrotoxicity of semustine (methyl-CCNU) has been studied in 45 adult patients with surgically resected Stage I or II malignant melanoma who received this drug as adjuvant chemotherapy. Abnormalities of renal function (including three cases of renal failure) were noted in seven of 45 patients (16 percent); all these patients received more than 1,400 mg/m2. This represents an incidence of 26 percent in patients receiving more than 1,400 mg/m2 of semustine. Two distinct patterns emerged. Abnormal serum creatinine levels developed in two patients while receiving semustine and later progressed to renal failure. Five patients had normal serum creatinine levels throughout their treatment courses but had abnormal creatinine values one month to two years following the completion of drug therapy. Renal failure developed in one of these patients, but the remaining four have had stable renal function for one to two years of additional follow-up. No clinical signs of renal insufficiency were detected in any patients receiving less than 1,400 mg/m2 of semustine. No changes unequivocally attributable to semustine were seen in eight patients at autopsy despite the fact that three had received greater than 1,900 mg/m2 of nitrosourea. This incidence of nephrotoxicity appears to be significantly lower than that previously reported in children. Guidelines for future therapy with semustine are described.

Adolescent↗

PubMed1983

Nephrotoxicity of semustine.

Semustine is an investigational cancer chemotherapeutic agent in widespread use. This agent has now been documented to produce nephrotoxicity and renal failure with long-term administration. We collected 29 cases of semustine nephrotoxicity from the literature and six unpublished cases brought to the attention of the National Cancer Institute. Using these 35 cases as a data base, we have analyzed the incidence, dose and treatment duration relationships, clinical and histologic manifestations, and clinical course of semustine nephrotoxicity. In addition, we discuss the possible mechanisms of this nephrotoxicity based upon ongoing laboratory work. We conclude that there is a high risk of severe nephrotoxicity from semustine when the cumulative dose exceeds 1200 mg/m2 and that there may be considerable delay in onset of the renal dysfunction.

Animals↗

PubMed1981

Response of metastatic cloacogenic carcinoma to treatment with semustine.

A case of cloacogenic carcinoma of the anorectal junction with pulmonary metastases is presented. Treatment with Semustine (Methyl-CCNU) resulted in a partial response lasting 15 months. Cloacogenic carcinoma is an uncommon neoplasm against which only a few chemotherapeutic agents have been tried. Semustine should be considered in the treatment of metastatic cloacogenic carcinoma.

Anus Neoplasms↗

PubMed1983

Leukemia and preleukemia after adjuvant treatment of gastrointestinal cancer with semustine (methyl-CCNU).

We evaluated the risk of acute nonlymphocytic leukemia, acute myelodysplastic syndrome, and preleukemia in 3633 patients with gastrointestinal cancer who were treated in nine randomized clinical trials. Among 2067 patients given semustine (methyl-CCNU) as adjuvant therapy, leukemic disorders developed in 14, whereas only one leukemic disorder (acute nonlymphocytic leukemia) occurred among 1566 patients given other therapies (relative risk = 12.4; 95 per cent confidence interval = 1.7 to 250). The six-year cumulative mean risk (+/- S.E.) of acquiring a leukemic disorder after treatment with semustine was 4.0 +/- 2.2 per cent; the incidence rate was 2.3 cases per 1000 persons per year. Risk increased significantly with time after treatment. The risk of leukemic disorders did not differ according to sex, race, age at treatment, or initial tumor type, nor was it enhanced by concomitant radiotherapy or immunotherapy. In addition, no excess of acute nonlymphocytic leukemia was seen in 44,370 patients treated for gastrointestinal cancer in Connecticut during the period 1935 to 1974, before the advent of nitrosourea chemotherapy. This study provides quantitative evidence that nitrosoureas are leukemogenic in human beings and confirms previous observations that adjuvant chemotherapy with alkylating agents may increase the risk of leukemia.

Acute Disease↗

PubMed1982

Combination chemotherapy of advanced colorectal cancer utilizing 5-fluorouracil, semustine, dacarbazine, vincristine, and hydroxyurea: a phase III trial by the Eastern Cooperative Oncology Group (EST: 4275).

Patients who had measurable evidence of recurrent or metastatic colorectal carcinoma following surgery and radiotherapy but no prior chemotherapy were randomized to one of five combination chemotherapy programs. Four of the treatments utilized five consecutive days of fluorouracil (FU) (days 1--5 and days 36--40) plus one oral dose of semustine (ME) (day 1) every ten weeks: (A) FU + ME; (B) FU + ME + vincristine (VC) (day 1 and day 36); (C) FU + ME + dacarbazine (DC) (days 1, 2, 36, 37); (D) FU + ME + VC + DC. The fifth treatment option(E) used a weekly treatment program of FU I.V. on day 1 plus hydroxyurea (HU) P.O. on day 4. The overall response rate was 13% (60/472) and the median survival time from start of therapy for all patients was 31 weeks. The response rate and the median survival time for each combination was (A) 9/103 = 9%, 26 weeks; (B) 10/92 = 11%, 28 weeks; (C) 15/101 = 15%, 37 weeks; (D) 11/91 = 12%, 27 weeks; (E) 15/85 = 18%, 38 weeks. There is no statistical difference in response rate or survival duration among any of the treatment options. The therapies containing DC produced the only complete responses (3 patients on treatment C and 2 on D). Treatment D was also associated with the longest median response duration (Treatment D = 55 weeks). Treatment A (FU + ME) was associated with the highest incidence of life-threatening toxicity.

Antineoplastic Agents↗

PubMed1988

Chemotherapy of malignant hepatomas with sequential intraarterial doxorubicin and systemic 5-fluorouracil and semustine.

Twenty patients with malignant hepatoma were treated with sequential intraarterial doxorubicin (72-hour continuous infusion) followed by systemic 5-fluorouracil (5-FU) and semustine (methyl CCNU). Objective tumor responses were seen in three patients (15%). The durations of response were 6, 19, and 27+ months, respectively. Median patient survival was 7 months. A variety of problems were encountered with the use of transcutaneous angiographic catheters for doxorubicin administration, including inability to adequately perfuse the liver, sepsis, and catheter dislodgement during chemotherapy infusion. Although some patients experienced palliation of reasonable duration, we do not believe that the overall results warrant further studies of this regimen.

Adult↗

PubMed1983

Combination chemotherapy containing semustine (MeCCNU) in patients with advanced colorectal cancer previously treated with 5-fluorouracil (5-Fu).

Two hundred thirty-two patients with advanced measurable colorectal cancer previously treated with 5-fluorouracil (5-Fu) were randomized to one of the following treatments: A) semustine (MeCCNU) plus vincristine (VCR); B) MeCCNU plus dacarbazine (DTIC); C) MeCCNU plus DTIC plus VCR; D) MeCCNU plus beta-2'-deoxythioguanosine (beta-TGdR). Platelet nadirs less than 50,000/mm3 were noted in 9% (Treatment A) to 19% (D) of the patients while WBC nadirs less than 2,000/mm3 were noted in 7% (B) to 12% (C,D) of the patients. Severe vomiting was noted in 2% (D) to 14% (B) of the patients. The partial response rates and median survival times from date of randomization were as follows: Treatment A: 3/54 (6%), 19 weeks; B: 9/59 (16%), 28 weeks; C: 3/60 (5%), 25 weeks; D: 2/59 (4%), 19 weeks. Differences in response rate and median survival are not statistically significant.

Antineoplastic Agents↗

PubMed1992

Radiation therapy and fluorouracil with or without semustine for the treatment of patients with surgical adjuvant adenocarcinoma of the rectum. Gastrointestinal Tumor Study Group.

PURPOSE: To evaluate the contribution of semustine (MeCCNU) to adjuvant benefit, previously untreated patients with histologically proven adenocarcinoma of the rectum who had undergone curative resection were randomized to treatment with combination radiation therapy and fluorouracil (5-FU) followed by either 12 months of 5-FU and MeCCNU or 6 months of escalating 5-FU. PATIENTS AND METHODS: Between March 1981 and November 1985, 210 patients were randomized by Gastrointestinal Tumor Study Group (GITSG) investigators. Subsequent to randomization, 11 (5%) patients (six treated with 5-FU and MeCCNU; five with escalating 5-FU) were found to be ineligible and are excluded from survival analyses. RESULTS: About half the patients on each of the two treatment arms experienced at least one episode of severe or worse toxicity, and there was one treatment-related death on each arm. No episodes of leukemia have been reported. Median follow-up time for surviving patients is 5.8 years, and 3-year follow-up is available for all but five surviving patients. Recurrent disease has been reported in 54% (51 of 95) of 5-FU- and MeCCNU-treated patients compared with 43% (45 of 104) of escalating 5-FU-treated patients. Probability of 3-year disease-free survival for the two treatment cohorts is 54% and 68%, respectively. Ninety-one deaths have occurred: 46% (44 of 95) of 5-FU- and MeCCNU-treated patients and 45% (47 of 104) of escalating 5-FU-treated patients. Three-year postsurgery survival probabilities are 66% and 75%. CONCLUSION: Substantial differences in survival or recurrence results between the two study arms are unlikely to be observed. We conclude that MeCCNU is not an essential component of effective postoperative combined modality treatment of adjuvant rectal cancer.

Adenocarcinoma↗

PubMed1986

Enhancement of semustine-induced cytotoxicity by chlorpromazine and caffeine in a human melanoma xenograft.

Chlorpromazine (CPZ) and caffeine (CFN) enhance the cytotoxicity of nitrosoureas in conventional murine tumor systems, but this effect was not confirmed in a randomized clinical trial which compared the action of semustine (MeCCNU) against the combination of MeCCNU, CPZ, and CFN. Since differences in repair systems are known to exist between cells of human or murine origin, we have employed a human melanoma xenograft system to quantify the drug interaction. The enhancement in human melanoma cells was similar to that observed with conventional murine tumor systems. Alkaline elution studies and determination of radioactivity from labeled MeCCNU pointed to increased drug retention and fixation of DNA damage as the mechanism of enhancement. Although toxicity studies were limited to murine tissues, there was evidence of increased toxicity, especially if MeCCNU was combined with both CPZ and CFN. Thus, a true therapeutic synergism may not be present for the combination. Some explanations for the failure to detect such drug interaction in clinical trials and the relevance of advanced preclinical tumor systems are discussed.

Animals↗

PubMed1984

Chemotherapy of advanced colorectal carcinoma: fluorouracil alone vs. two drug combinations using fluorouracil, hydroxyurea, semustine, dacarbazine, razoxane, and mitomycin. A phase III trial by the Eastern Cooperative Oncology Group (EST: 1278).

Patients with advanced colorectal cancer and no prior chemotherapy were randomized to six treatment regimens: A) fluorouracil (FU) alone; B) FU + hydroxyurea (HU); C) semustine (SE) + dacarbazine (DA); D) FU + HU alternating with SE + DA; E) SE + razoxane (RA); F) mitomycin (MI) + DA. There were no significant treatment differences with respect to response, which ranged from 9-23% (overall 32/207 or 15%) or median survival duration, which ranged from 17 weeks to 32 weeks. Patients treated with FU or FU + HU experienced substantially less toxicity than those on the other treatment arms.

Adenocarcinoma↗

PubMed1983

Phase I evaluation of semustine in a weekly schedule.

A phase I study of weekly semustine was conducted in 32 patients with advanced cancer. Doses were escalated from 18 to 36 mg/m2/week. At a dose of 36 mg/m2/week, 43% of the patients developed platelet counts less than 100,000/mm3 after a median of 20 weeks on study, and 25% developed wbc counts less than 3000/mm3 after a median of 16 weeks on study. Drug-related nausea was reported by only one patient and was the only subjective toxic effect reported. Tumor regressions were noted in patients with adenocarcinoma of the colon, melanoma, and mixed adenocarcinoma and squamous cell lung cancer. A reasonable starting dose for phase II studies is 36 mg/m2/week, with dose adjustments based on platelet and wbc counts.

Dose-Response Relationship, Drug↗

PubMed1982

Phase II study of mitolactol and semustine combination chemotherapy for advanced malignant melanoma.

Twenty-six patients with disseminated malignant melanoma received an oral regimen of mitolactol and semustine (methyl-CCNU). Sixteen patients had received prior systemic therapy, and 16 had visceral involvement. There were no objective regressions among ten patients receiving the drugs as initial systemic therapy. However, one of 16 patients having prior systemic treatment did have an objective response. Hematologic and gastrointestinal toxic effects were well-tolerated.

Aged↗

PubMed1982

Phase I--II study of the combination of 5-FU, doxorubicin, mitomycin, and semustine (FAMMe) in the treatment of adenocarcinoma of the stomach, gastroesophageal junction, and pancreas.

One hundred and fifteen patients with advanced gastrointestinal cancer (stomach cancer, 42 patients; gastroesophageal junction cancer, ten; pancreatic cancer, 32; and other upper gastrointestinal cancers, 31) were treated with a combination chemotherapy regimen consisting of 5-FU, doxorubicin, mitomycin, and semustine (methyl-CCNU) (FAMMe). Of the 31 patients with stomach cancer who were evaluable for response and had had no previous chemotherapy, 12 (39%) achieved complete or partial remission. One of eight (12%0 patients with gastroesophageal junction cancer and five of 23 (22%) patients with pancreatic cancer achieved a partial remission. The median duration of survival for all patients with adenocarcinoma of the stomach was 7.1 months. The median duration of survival for responding patients with stomach cancer was 13.6 months, and the median survival for nonresponding patients was 6.1 months. FAMMe chemotherapy was generally well-tolerated and can be administered in adequate doses without producing prohibitive myelosuppression. The starting dose should be reduced for patients greater than or equal to 70 years old or for patients who have received pelvic or vertebral radiation therapy. FAMMe is effective against advanced gastric cancer; however, because this was not a randomized comparative study of the relative effectiveness of FAMMe and FAM (5-FU, doxorubicin, and mitomycin), no recommendation for the use of one regimen instead of the other for advanced adenocarcinoma of the stomach can be made. FAMMe chemotherapy cannot recommended for advanced adenocarcinoma of the pancreas and gastroesophageal junction.

Adenocarcinoma↗

PubMed1984