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Phase II trial of 5-FU, vincristine, and mitomycin (FOMi) in metastatic bronchioloalveolar cell lung cancer: a Southwest Oncology Group Study.

Twenty-three previously untreated patients with bronchioloalveolar cell lung cancer who had measurable disease and distant metastases (stage IIIM1, extensive) were treated with combination chemotherapy including 5-FU, vincristine, and mitomycin. Two of 23 patients (9%) achieved partial response lasting 5 and 6 months. Two patients (9%) died of sepsis while neutropenic. The current study does not justify the use of 5-FU, vincristine, and mitomycin combination chemotherapy in patients with metastatic bronchioloalveolar cell lung cancer.

Adenocarcinoma, Bronchiolo-Alveolar↗

BCG (RIVM) versus mitomycin intravesical therapy in superficial bladder cancer. First results of randomized prospective trial.

This study presents the preliminary results of a randomized prospective two-arm study in which bacillus Calmette-Guérin (BCG) RIVM, a Dutch BCG preparation, is compared with mitomycin C (MMC) in patients with primary or recurrent superficial bladder tumors, including carcinoma in situ (CIS). Therapeutic regimens were as follows: after complete transurethral resection of all visible tumors, BCG RIVM (1 x 10(9) bacilli in 50 mL saline) was instilled once a week for six consecutive weeks, and mitomycin C (30 mg in 50 mL saline) was administered once a week for one month (weeks 1 to 4) and thereafter once a month for a total of six months. Reported are the incidence of side effects in 165 patients and the recurrence rate of tumors in 308 patients after a follow-up period of twelve months. Drug-induced, or chemical cystitis was observed in 13 (16.7%) of 78 BCG-treated patients and in 12 (13.8%) of 87 MMC-treated patients. In the same groups bacterial cystitis occurred in 17 (21.8%) patients and in 16 (18.4%) patients, respectively. In the BCG-treated group (N = 148), 44 (29.8%) had recurrent tumors, while in the MMC-treated group (N = 160), 40 (25.0%) had a recurrence. The recurrence rate for BCG-treated patients was 0.33; the recurrence rate for MMC-treated patients was 0.29 (P = 0.560, not significant). These preliminary data demonstrated no statistically significant difference between the two arms with regard to toxicity and recurrence of tumors.

Administration, Intravesical↗

Long duration of response with vindesine-mitoxantrone-mitomycin (VMMc) combination chemotherapy in metastatic breast cancer: a pilot phase II study.

A total of 39 women with metastatic breast cancer entered a pilot phase II study of the vindesine-mitoxantrone-mitomycin (VMMc) combination chemotherapy. Most of them had received previous chemotherapy [including doxorubicin (27 patients)] for their primary or metastatic disease. The VMMc drugs were given at usual doses. Hematologic side effects were the most serious, leading mainly to leukopenia (five episodes of infection were successfully treated). A 33% partial response rate was obtained (95% confidence limits, 18%-48%), with a median duration (not yet reached) of greater than 510 days (range, 150-720) for the overall population. The median for pretreated patients was greater than 420 days (range, 150-720) which compares favorably with those previously reported in similar patients treated by mitomycin and vindesine or vinblastine.

Adult↗

Treatment of advanced gastric carcinoma with mitomycin and doxorubicin.

Thirty patients with advanced gastric carcinoma were treated with doxorubicin combined with mitomycin; only four (13%) responded. Myelosuppression was the major toxic effect; there was one toxic death. The overall median survival was 14 weeks (range, 2-42), which is no different from that reported for untreated patients. The combination of doxorubicin and mitomycin alone cannot be recommended for use in patients with advanced gastric carcinoma.

Adenocarcinoma↗

Mitomycin for patients who have failed on thiotepa. The National Bladder Cancer Group.

The National Bladder Cancer Group undertook a study to determine the effectiveness and toxicity of mitomycin in patients who failed on thiotepa. A total of 117 patients with residual superficial transitional cell bladder cancer (Ta, T1, Tis) who had previously failed on intravesical thiotepa were treated with 40 mg of mitomycin instilled intravesically weekly for eight weeks. Four to six weeks after the last treatment, tumor response was evaluated by cystoscopy, biopsy of the site of the index lesion, and cytology. In 57 patients (48.7%), visible tumor had been ablated. Results of cystoscopy, biopsy, and cytology were negative in 32 (27.4%) patients. Eleven patients (9.4%) had no visible tumor and negative cytology unconfirmed by biopsy. In 14 patients (12%) who had complete destruction of the tumor at cystoscopy, and biopsy specimen was negative for tumor, cytology was positive, indicating a partial response. Six patients (5.1%) withdrew from the study before the first evaluation because of local toxicity (cystitis).

Administration, Topical↗

Adriamycin, mitomycin C, and 5-fluorouracil in combination for advanced colorectal adenocarcinoma previously treated with 5-fluorouracil.

Twenty-one patients with progressing colorectal carcinoma previously treated with 5-FU were given a combination of 5-FU, adriamycin, and mitomycin C in an attempt to produce an objective response. No response was observed; 24% of patients had an arrest of their disease for a median of 18 weeks. 5-FU, adriamycin, and mitomycin C in combination failed to produce a response in patients with colorectal carcinoma previously treated with 5-FU.

Adenocarcinoma↗

Fatal acute respiratory failure after vinblastine-mitomycin therapy in lung carcinoma.

The occurrence of pulmonary toxic reaction due to vinblastine sulfate alone or in combination with drugs other than mitomycin is not known. Acute respiratory distress is a rare phenomenon in patients receiving both chemotherapeutic agents. Two cases of fatal acute respiratory failure due to pulmonary edema occurred in patients receiving vinblastine-mitomycin for non-small-cell carcinoma of the lung. In view of the unpredictability of the reaction, observation of patients receiving this combination therapy is recommended.

Acute Disease↗

Effects of tryptophan analogs, mitomycin C and acridine orange on the production of filtrable hemolysin by Escherichia coli.

Bacteriostatic doses of 5-methyltryptophan and of 7-azatryptophan exert a complete inhibition on the in vitro production of filtrable hemolysin by Escherichia coli. This inhibition is readily overcome by L-tryptophan, and does not seem to be specific but secondary to an interference with de novo protein synthesis and cell multiplication as is observed with chloramphenicol in sensitive strains. Although the influence of the two tryptophan analogs on hemolysin production and cell multiplication is similar, their mechanism of action at the molecular level appears to be different. The addition of 50 microg/ml 7-azatryptophan which causes an unbalanced growth characterized by an arrest of the cellular division and an increase of cell size, blocks the production of an active hemolysin. Exposure to 4 microg/ml 5-methyltryptophan also prevents cell multiplication and hemolysin production but no sign of unbalanced growth is evident. Mitomycin C in concentrations sufficient to prevent increase in the number of viable units provokes an extreme elongation of E. coli cells and, apparently, does not stop the synthesis of hemolysin. In blocking the production of hemolysin the three inhibitors of protein synthesis used in this study were more effective than mitomycin C an agent known to affect deoxyribonucleic acid synthesis and to induce extrachromosomic genetic factors. Results of conjugation experiments also described here support the finding of other workers that the genetic factor that controls the production of the filtrable hemolysin in E. coli can be transmitted by conjugation. Acridine orange eliminated the hemolytic property from a large proportion of the population of a hemolytic strain which did not carry the R factor, but was little effective in the strains which had received both the R factor and the hemolytic character by conjugation.

Acridines↗

Bleomycin, vincristine, and mitomycin C with or without methotrexate in the treatment of squamous cell carcinoma.

Forty-two patients with metastatic squamous cell carcinoma were treated with bleomycin, vincristine, and mitomycin C with or without methotrexate (BOM +/- M). The overall response rate of 64% (complete response [CR] rate, 19%) included 19 responses among 26 patients (seven CRs) with head and neck cancer, three responses among eight patients with cervical cancer, and three responses among five patients (one CR) with lung cancer. Six of 12 patients (two CRs) responded to BOM and 21 of 30 patients (six CRs) responded to BOMM. The median duration of response was 16 weeks. Toxic effects included nausea or vomiting in 33% of the patients, fever of > 101 degrees C in 26%, stomatitis in 29% and pulmonary toxicity in 19%. Four of eight cases of pulmonary toxicity were fatal and the incidence was related to the amount of both bleomycin and mitomycin C administered. The occurrence of pulmonary toxicity could not be predicted by serial determination of pulmonary function or blood gases. A wbc count nadir of < 2500/mm3 occurred in 15 of 42 patients. There were two episodes of sepsis with one death. A platelet count nadir of > 75,000/mm3 occurred in eight of 42 patients with no episodes of hemorrhage. BOMM produces a high objective response rate in patients with squamous cell cancer. However, the duration of remission is brief, and use of the regimen carries an increased risk of fatal pulmonary toxicity.

Adult↗

Effect of peplomycin plus carbazilquinone and mitomycin on non-small cell carcinoma of the lung.

The effects of two chemotherapeutic regimens, peplomycin (PLM) plus carbazilquinone and PLM plus mitomycin, on non-small cell carcinoma of the lung were evaluated by a randomized controlled trial. Seven partial responses were observed in 53 evaluable patients, for an overall response rate of 13.2%. There was no difference in response rate or in median survival time between PLM plus carbazilquinone (11.5% and 32 weeks) and PLM plus mitomycin (14.8% and 25 weeks). Seven patients developed interstitial pneumonitis, and four died of pulmonary fibrosis. It was concluded that the chemotherapeutic regimens that include PLM are only marginally effective against non-small cell carcinoma of the lung, with relatively frequent pulmonary fibrosis.

Adenocarcinoma↗

Extensive adenocarcinoma and large cell undifferentiated carcinoma of the lung treated with 5-FU, vincristine, and mitomycin C (FOMi).

Fifty-six patients with extensive (52 with TNM stage III M1 disease and four with TNM stage III M0 disease) adenocarcinoma (46 patients) and large cell undifferentiated carcinoma (ten patients) of the lung were treated with combination chemotherapy consisting of 5-FU, vincristine, and mitomycin C (FOMi). The patients had not received prior chemotherapy. The overall response rate was 41% (23 of 56 patients). Four patients achieved a complete response and 19 achieved a partial response. In 12 patients the disease was stable. Response did not vary by cell type: adenocarcinoma, 18 of 43 patients (42%); large cell carcinoma, four of ten (40%); and alveolar cell carcinoma, one of three (33%). The response varied by initial performance status. For a Karnofsky score of greater than or equal to 70%, 20 of 41 patients (49%) responded, while for a Karnofsky score of less than 70%, three of 15 patients (20%) responded (P = 0.22). Survival was improved for responding patients regardless of initial performance status. The median survival duration was 24 weeks for the entire group of patients treated with FOMi. Survival of the responders (complete response plus partial response) was significantly improved over that of patients with progressive disease (28 weeks versus 13 weeks, respectively; P = 0.002). The FOMi combination was very well-tolerated. Nausea was common, but vomiting occurred in only four of 56 patients. Thrombocytopenia, requiring a reduction in the mitomycin C dose, developed after the third treatment course in 14 patients.

Adenocarcinoma↗

Mitomycin-associated renal failure. Case report and review.

Renal failure due to mitomycin chemotherapy is a poorly appreciated entity often associated with microangiopathic hemolytic anemia. We describe a 45-year-old man in whom renal failure and anemia developed, without evidence of hemolysis, five months after beginning chemotherapy with mitomycin, fluorouracil, and doxorubicin hydrochloride. A biopsy specimen taken from the patient's kidney showed fibrin thrombi in two of 18 glomeruli and in several small arteries. The patient's condition required institution of maintenance dialysis. Similar reports from the literature are reviewed.

Adenocarcinoma↗

Chemotherapy for metastatic non-small cell bronchogenic carcinoma: cyclophosphamide, doxorubicin, and etoposide versus mitomycin and vinblastine (EST 2575, generation IV).

Between March and December 1979, the Eastern Cooperative Oncology Group (ECOG) compared the CAVP16 (cyclophosphamide, doxorubicin, and etoposide) and MV (mitomycin and vinblastine) regimens in 200 patients with metastatic non-small cell bronchogenic carcinoma. Most patients were ambulatory (ECOG performance status, 0, 1; 75%) and had not received prior radiation therapy (76%). The CAVP16 regimen resulted in one complete and 13 partial responses (14%) and the mitomycin and vinblastine regimen resulted in two complete and 11 partial responses (13%). These results did not differ significantly (P = 0.45) nor did the results for median survival, 18 weeks for each regimen. Good performance status and prior surgical resection were positive predictors of improved survival. Toxicity was significant with eight drug-related deaths, six due to leukopenia and infection and one each due to renal failure and interstitial pneumonitis. CAVP16 resulted in significantly more serious and life-threatening toxicity (P less than 0.0001). Neither regimen is recommended for further study.

Aged↗

Studies on the suppression of a one-way mixed lymphocyte reaction by mitomycin-C treated responder cells.

We have investigated the suppression of lymphocyte proliferation in a one-way mixed lymphocyte culture by autologous mitomycin-C treated responder cells. The suppression was proportional to the number of mitomycin-C treated cells added. Irradiated cells suppressed in the same manner. Using subpopulations of peripheral blood mononuclear cells, it was shown that the 'suppressor activity' was not confined to a particular subpopulation, but was exhibited by all subpopulations tested. Cycloheximide-treated peripheral blood mononuclear cells and autologous erythrocytes also suppressed. These results suggest that 'suppression' in this system is due to mechanical interference by the added cells. The implications for the design of assays for spontaneous suppressor cell activity in man are discussed.

Adult↗

Reduced mitomycin C induces heat-labile sites in DNA at specific sequences.

We have investigated the sequence specificity of DNA damage induced by mitomycin C reduced with NaBH4, by using 3'- or 5'-end labeled DNA fragments of defined sequence. Mitomycin C reduced with NaBH4 induced heat-labile sites in DNA preferentially at specific sequences. The most preferred trinucleotide sequence for induction of heat-labile sites was GGT, followed by GGG, AGT, GAG, GGC and AGG. Active oxygens such as hydroxyl radical and singlet oxygen, and metal ions were involved in the induction of heat-labile sites. DNA was broken at the 3' side of deoxyguanosines and some of deoxyadenosines by heat-treatment. The produced oligonucleotides contained phosphoryl groups at the 5' termini. The 3' termini seemed not to have simple structures.

Base Sequence↗

Dyspnea following vinblastine or vindesine administration in patients receiving mitomycin plus vinca alkaloid combination therapy.

Pulmonary toxicity is not commonly associated with the vinca alkaloids vinblastine and vindesine. Three patients receiving the combination of mitomycin plus vindesine or vinblastine developed acute dyspnea 1-5 hours following vinca alkaloid administration. Two of the three patients continued to receive therapy and both experienced symptoms with each subsequent vinblastine or vindesine injection. No other cause for the dyspnea could be detected. We conclude that, as in the three previously reported cases, shortness of breath can occur after the injection of vinblastine or vindesine in patients receiving mitomycin plus vinca alkaloid combination therapy.

Antineoplastic Combined Chemotherapy Protocols↗

An evaluation of hexamethylmelamine, cis-diamminedichloroplatinum, and mitomycin-C in advanced breast cancer. A pilot study of the Southeastern Cancer Study Group.

Eleven patients with metastatic breast cancer refractory to conventional therapy were treated with a combination of hexamethylmelamine 250 mg/m2 p.o. days 1-14, repeated at 4-week intervals; cis-platinum 30 mg/m2 I.V. q 28 days; and mitomycin-C 7.5-10 mg/m2 I.V. q 56 days. There were no complete responders and three partial responders for a response rate of 27%. Two patients (18%) had stabilization of disease for brief periods. The gastrointestinal toxicity of hexamethylmelamine was unacceptable. Recent reports that cis-platinum and hexamethylmelamine lack activity in breast cancer suggest that the activity of the combination was due to mitomycin-C alone.

Altretamine↗