Sister chromatid exchanges in lymphocytes of cancer patients receiving mitomycin C treatment.

Peripheral lymphocytes from cancer patients receiving mitomycin C treatment were examined for cytogenetic effects. The treatment consisted of i.v. injections of mitomycin C at a dose of 4 mg given twice a week for 2 weeks. The lymphocytes were cultured in vitro for 72 hr with phytohemagglutinin and 5-bromodeoxyuridine, and then sister chromatid exchanges were scored. Before treatment with mitomycin C, the frequencies of sister chromatid exchanges in lymphocytes of cancer patients were similar to those of healthy controls. After the first and second treatments in vivo with mitomycin C, the frequencies of sister chromatid exchnages increased with time, reached a peak in about 24 hr, and then returned to the pretreatment level in about 48 hr, in contrast to the case of in vitro exposure to mitomycin C. After the third and fourth injections, however, the frequency increased further and did not return to the original level. The significance of the specific kinetics of change in the sister chromatid exchnage frequency after in vivo treatments is discussed in relation to cancer chemotherapy.

Metabolism of mitomycin C by DT-diaphorase: role in mitomycin C-induced DNA damage and cytotoxicity in human colon carcinoma cells.

The role of DT-diaphorase in bioreductive activation of mitomycin C was examined using HT-29 and BE human carcinoma cells which have high and low levels of DT-diaphorase activity, respectively. HT-29 cells were more sensitive to mitomycin C-induced cytotoxicity than the DT-diaphorase-deficient BE cell line. Mitomycin C induced DNA interstrand cross-linking in HT-29 cells but not in BE cells. Both mitomycin C-induced cytotoxicity and induction of DNA interstrand cross-links could be inhibited by pretreatment of HT-29 cells with dicoumarol. Metabolism of mitomycin C by HT-29 cell cytosol was pH dependent and increased as the pH was lowered to 5.8, the lowest pH tested. Metabolism of mitomycin C by HT-29 cytosol was inhibited by prior boiling of cytosol or by the inclusion of dicoumarol. Little metabolism was detected in BE cytosols. When purified rat hepatic DT-diaphorase was used, metabolism of mitomycin C increased as the pH was decreased and could be detected at pH 5.8, 6.4, 7.0, 7.4, but not at 7.8. Metabolism of mitomycin C was NADH dependent and inhibited by dicoumarol or by prior boiling of enzyme. An approximate 1:1 stoichiometry between NADH and mitomycin C removal was demonstrated and no oxygen consumption could be detected. Metabolism of mitomycin C by purified HT-29 DT-diaphorase was also dicoumarol inhibitable and pH dependent. The major metabolite formed during metabolism of mitomycin C by HT-29 cytosol, purified HT-29, and rat hepatic DT-diaphorase was characterized as 2,7-diaminomitosene. These data suggest that two-electron reduction of mitomycin C by DT-diaphorase may be an important determinant of mitomycin C-induced genotoxicity and cytotoxicity.

Cancer-associated hemolytic-uremic syndrome: analysis of 85 cases from a national registry.

A registry of suspected cases of cancer-associated hemolytic-uremic syndrome (C-HUS) was established in May 1984. Records of 85 patients from the registry, all with history of cancer, hematocrit less than or equal to 25%, platelet count less than 100,000, and serum creatinine greater than or equal to 1.6 mg/dL were subjected to in-depth analysis. Eighty-nine percent of patients had adenocarcinoma, including 26% with gastric cancer. Microangiopathic hemolysis was reported in 83 patients; coagulation studies were normal with rare exception. Bone marrow examination ruled out chemotherapy-induced myelosuppression in 68 of 85. Thirty-five percent of patients were without evident cancer at time of syndrome development. Mitomycin (MMC) was part of the treatment regimen in 84 patients; all but nine received a cumulative dose greater than 60 mg. Pulmonary edema, generally noncardiogenic, developed in 65% of patients, often after blood product transfusions. C-HUS has a high mortality: over 50% of patients died of or with syndrome, most within 8 weeks of syndrome development. Conventional treatment was ineffective, although ten of 21 treated with staphylococcal protein A (SPA) immunopheresis showed significant responses. Statistical analysis found only absence of obvious tumor and treatment with SPA to suggest favorable prognosis. C-HUS is distinguishable from related syndromes such as childhood HUS, thrombotic thrombocytopenic purpura (TTP), consumption coagulopathy, and microangiopathic hemolysis associated with advanced carcinoma. MMC is likely involved in the development of C-HUS; the risk of developing C-HUS after treatment with MMC is between 4% and 15%. However, possible bias in patients referred to the registry and reports of non-MMC C-HUS cases must be remembered. Recommendations include careful monitoring of renal and hematologic function in patients treated with MMC, aggressive nontransfusion in patients with suspected C-HUS, and consideration of treatment with SPA immunopheresis in patients with definite syndrome.

Treatment of advanced breast cancer with mitomycin C combined with vinblastine or vindesine.

Mitomycin C together with either vindesine or vinblastine was given to 48 patients with previously treated advanced breast cancer. Thirteen (35%) of the 37 evaluable patients had a complete (one patient) or partial (12 patients) response. Overall median duration of response was 189 days (range, 90-700 days). Fifteen patients received mitomycin C and vindesine with six responses (40%) and a median response duration of 247 days (range, 162-700 days). Twenty-two patients received mitomycin C and vinblastine with seven responses (32%) and median response duration of 164 days (range, 90-330 days). Response duration for patients treated with mitomycin C plus vindesine was longer than that associated with mitomycin C plus vinblastine (p = 0.09). Significant toxicity included myelosuppression and neurologic symptoms, but was uncommon (less than 10% of patients). Therefore, the combination of mitomycin C and a vinca alkaloid appears to be useful in far-advanced refractory breast cancer.

Combination chemotherapy for locally advanced pancreatic cancer: equivalence to external beam irradiation and implication for future management.

Chemotherapy with 5-fluorouracil, doxorubicin, and mitomycin-C was administered to 17 patients with locally advanced pancreatic cancer. The median survival for these patients was 8 months. With a multiaxial retrospective analysis, the overall survival of this study group appears to be least equivalent to that reported with 6,000 photon rad alone or of neutrons, and compares favorably to that achieved with combined 6,000 photo rad plus 5-fluorouracil. Of 15 relapses, only 4 had presented with evidence of disseminated disease. Based upon this analysis we recommend additional studies of combination chemotherapy with radiation therapy in future prospective randomized trials.

5-Fluorouracil, mitomycin, and doxorubicin (FAM) in carcinoma of the biliary tract.

A phase II trial of the regimen 5-fluorouracil, doxorubicin, and mitomycin C (FAM) was conducted in 17 patients with advanced or recurrent biliary tract cancer. Among 14 patients with measurable disease, 31% achieved a partial response. An additional seven patients evidenced stabilization of disease for periods of three to 18+ months. One patient with advanced but unmeasurable tumor has survived 72 months after 12 cycles of treatment. There was no serious life-threatening toxicity, and with appropriate dosage adjustment, the drug was administered to patients with mild hepatic insufficiency. We recommend the initiation of a larger controlled trial and a potential application with radiotherapy for patients with less advanced disease.

Pelvic intra-arterial mitomycin C infusion in previously treated patients with metastatic, unresectable, pelvic colorectal cancer and angiographic determination of tumor vascularity.

Thirty patients with unresectable pelvic tumors from recurrent or metastatic colorectal cancer, after failing all conventional chemotherapy or radiotherapy, were treated with mitomycin C (MMC) regional intra-arterial (IA) infusion. MMC at a dose of 20 mg/m2 in 100 mL of 5% dextrose in water was infused for a one-hour period through the regional artery (eg, hypogastric, gluteal) approached percutaneously via the femoral artery. This treatment was repeated every four to eight weeks. Of the 26 patients who could be evaluated, three had objective responses, 14 had tumor stabilization, and nine had no response. Median survival time for the responders (Rs) was 435 days, for stabilized patients (Ss) was 263 days, and for nonresponders (NRs) was 195 days, giving an overall survival time of 239 days. Fourteen patients (2 Rs, 8 Ss, and 4 NRs) had good relief of pain after the IA infusion. Thirty-three pelvic arteriograms (including three patients who had never received IA infusion) showed an avascular tumor of grade 0 in eight patients, a hypovascular tumor of grades 1 and 2 in 16 patients, and a vascular tumor of grade 3 in nine patients. Neovasculatures were mainly derived from the hypogastric artery or its branches (eg, gluteal, obturator, and pudendal artery), and occasionally were found to be derived from the superior hemorrhoidal, lumbar, and sacral arteries. The major side effect after the pelvic infusion was necrotizing cellulitis occurring in the buttock. Myelosuppression was manageable and other toxic effects were mild. Metastatic colorectal cancer occurring in the pelvis was basically a vascular-deficient tumor. Regional IA MMC infusion given intermittently was found effective in palliating pelvic pain and improving the quality of these patients' lives.

Phase II study of concurrent radiotherapy and chemotherapy for unresectable stage III non-small-cell lung cancer. Southern Osaka Lung Cancer Study Group.

PURPOSE: To evaluate the response rate, toxicity, and 2-year survival rate of concurrent radiotherapy and chemotherapy for unresectable stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between July 1989 and October 1990, 65 patients with histologically or cytologically proven unresectable stage III NSCLC without T3N0-1M0 disease were entered onto this study. Sixty-one patients were eligible for response, survival, and toxicity analysis. Chemotherapy consisted of vindesine (3 mg/m2 on days 1, 8, 29, and 36), cisplatin (100 mg/m2 on days 1 and 29), and mitomycin (8 mg/m2 on days 1 and 29). Radiotherapy was administered for 3 weeks (2 Gy given 13 times, five fractions per week), followed by 10-day rest periods and then the previous schedule of radiotherapy repeated for 3 weeks. RESULTS: Of 61 eligible patients, 53 (86.9%) had a partial response (PR). The median response duration was 39.1 weeks (range, 8.4 to 163+). The median survival time was 16 months and the 2-year survival rate was 36.7%. Of 53 responding patients, 10 (16.4%) are alive and disease-free after 2 years. The major toxicity was leukopenia (> or = grade 3, 95%). Other toxicities of > or = grade 3 included thrombocytopenia (45%), anemia (28%), nausea/vomiting (16%), fever (11%), and esophagitis (6%). Treatment-related death occurred in two patients. One patient died of pulmonary toxicity (interstitial pneumonitis) and the other of esophagobronchial fistula with pulmonary infection. CONCLUSION: Concurrent radiotherapy plus chemotherapy with mitomycin, vindesine, and cisplatin (MVP) can be safely administered to patients with stage III NSCLC, with excellent response rates and 2-year survival rates.

5-fluorouracil, adriamycin, and mitomycin in the treatment of adenocarcinoma of unknown primary.

The combination of 5-fluorouracil (5-FU), doxorubicin, and mitomycin (FAM) is often recommended for empiric management of patients with adenocarcinoma of unknown primary. This recommendation is based on the activity of FAM for adenocarcinomas of specific known sites of origin. A literature search disclosed no reports of the efficacy of FAM in this clinical entity. We report on 45 patients with biopsy-proven adenocarcinoma in whom investigation revealed no primary site and who were treated in a phase II trial with FAM. Of 43 evaluable patients, four achieved a complete tumor response, and nine obtained a partial response for an overall response rate of 30%. The median survival for all patients was greater than 10 months. The median survival for patients whose tumors were unresponsive to FAM was 6 months, and median survival was greater than or equal to 14 months in patients with stable disease or FAM-responsive tumors. A phase III trial comparing no therapy or 5-FU with FAM is warranted. For patients not treated in an investigative setting, FAM compares favorably with reported series using other regimens.

Phase II randomized trial of cisplatin chemotherapy regimens in the treatment of recurrent or metastatic squamous cell cancer of the cervix: a Southwest Oncology Group Study.

Cisplatin has proven to be the most active single agent in the treatment of metastatic and recurrent squamous cell cancer of the cervix. In a previous southwest Oncology Group (SWOG) pilot study, the addition of cisplatin to a mitomycin-C, vincristine, and bleomycin (MVB) regimen resulted in a relatively high percentage of durable complete responses. To gain more experience with cisplatin-based chemotherapy regimens, the SWOG initiated a phase II randomized trial of cisplatin, mitomycin-C plus cisplatin (MC), and MVB plus cisplatin (MVBC) in 119 patients with advanced squamous cell cancer of the cervix and no prior chemotherapy exposure. Because of slow patient accrual early in the trial, the cisplatin arm was discontinued. Five patients were declared ineligible according to protocol criteria. The three treatment groups were relatively well matched for age, prior radiation exposure, and sites of measurable disease. The overall objective response rates for cisplatin, MC, and MVBC treated patients were 33%, 25%, and 22%, respectively. Median response durations were greater than 6 months. Median survival durations associated with cisplatin, MC, and MVBC treatment were 17.0, 7.0, and 6.9 months, respectively. There were no drug-related deaths. Severe or life-threatening leukopenia and thrombocytopenia were observed in 18% to 24% of patients treated with MVBC and MC, but in none of those receiving cisplatin alone. We conclude that the low response rates and short durations of both response and survival observed in patients randomized to the two chemotherapy combinations suggest that only enhanced toxicity was gained through the addition of mitomycin-C or MVB to cisplatin in patients with advanced cervix cancer.

Inefficacy of dacarbazine, mitomycin C, and hepatic irradiation in patients with metastatic adenocarcinoma of the gastrointestinal tract.

A regimen combining hepatic irradiation and intravenous dacarbazine and mitomycin C for treating colorectal adenocarcinoma with liver metastases offers no advance in the management of patients with this disease.

Randomized comparison of two combination regimens versus minimal chemotherapy in nonsmall-cell lung cancer: a Southeastern Cancer Study Group Trial.

Patients with advanced nonsmall-cell lung cancer (NSCLC), good performance status, and no prior chemotherapy were randomized to receive one of three regimens: intravenous vindesine (V) 3 mg/m2 every 2 weeks; V 3 mg/m2 weekly for 5 weeks, followed by a dose every 2 weeks plus mitomycin (VM) 20 mg/m2 day 1 and then 15 mg/m2 every 6 weeks; or V at the more intensive dose rate plus cisplatin (VC) 120 mg/m2 with forced diuresis on days 1 and 29 and then every 6 weeks. A total of 435 patients were enrolled in the trial, with 410 (94%) assessable for prognostic characteristics and survival. Among the 375 patients assessable for response, only 58 (15%) achieved objective response. Single-agent V every 2 weeks was inactive (response rate less than 1%), effectively acting as a no-treatment arm. Among assessable patients receiving VM, 33 (27%) responded; among patients receiving VC, 24 (19%) responded. There was no statistically significant survival difference among the treatment arms, with median survival among those treated with V 14.8 weeks, VM 20.4 weeks, and VC 24.7 weeks; VC achieved borderline significance (P = .06) compared with V. In a prognostic factor analysis, treatment was not a significant factor (P = .447) for survival. Thus, in this large multicenter trial, neither a high-dose cisplatin combination nor a noncisplatin regimen (VM) with a comparable response rate had a significant survival advantage over minimal chemotherapy. New approaches are needed in advanced NSCLC.

A phase II trial of pleurectomy/decortication followed by intrapleural and systemic chemotherapy for malignant pleural mesothelioma.

PURPOSE: This study investigated the feasibility of a novel approach to the treatment of malignant pleural mesothelioma by combining surgical resection with immediate postoperative intrapleural chemotherapy and subsequent systemic chemotherapy. PATIENTS AND METHODS: Patients with biopsy-proven, resectable malignant pleural mesothelioma underwent pleurectomy/decortication immediately followed by intrapleural chemotherapy with cisplatin 100 mg/m2 and mitomycin 8 mg/m2. Systemic chemotherapy was started 3 to 5 weeks postoperatively and included cisplatin 50 mg/m2 on days 1, 8, 15, 22, 36, 43, 50, and 57, and mitomycin 8 mg/m2 on days 1 and 36. Patients were then monitored by serial chest and abdominal computed tomographic (CT) scans every 3 months until death or for a minimum of 18 months, whichever occurred first. RESULTS: Of 36 patients entered onto the study, 28 had pleurectomy/decortication and intrapleural chemotherapy. There was one postoperative death, and two episodes of grade 4 renal toxicity after intrapleural chemotherapy. The 23 patients who also had systemic chemotherapy received a median of 80% and 87% of the planned total cisplatin and mitomycin doses, respectively. No grade 3 or 4 toxicities were observed. The overall survival rate of the 27 patients who were originally candidates for systemic chemotherapy was 68% at 1 year and 40% at 2 years, with a median survival duration of 17 months. Locoregional disease was the most common form of relapse (16 of 20 patients). CONCLUSION: This short but aggressive combined modality regimen was generally well tolerated, but should not be used outside of a protocol setting because of the potential for serious toxicity. Overall survival was as good or better than with previously reported multimodality approaches, but other strategies are needed to improve local control.

Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer.

PURPOSE: We report the results of a prospectively randomized study that compared the combination of epirubicin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) (ECF) with the combination of mitomycin, cisplatin, and PVI 5-FU (MCF) in previously untreated patients with advanced esophagogastric cancer. PATIENTS AND METHODS: Five hundred eighty patients with adenocarcinoma, squamous carcinoma, or undifferentiated carcinoma were randomized to receive either ECF (epirubicin 50 mg/m(2) every 3 weeks, cisplatin 60 mg/m(2) every 3 weeks and PVI 5-FU 200 mg/m(2)/d) or MCF (mitomycin 7 mg/m(2) every 6 weeks, cisplatin 60 mg/m(2) every 3 weeks, and PVI 5-FU 300 mg/m(2)/d) and analyzed for survival, response, toxicity, and quality of life (QOL). RESULTS: The overall response rate was 42.4% (95% confidence interval [CI], 37% to 48%) with ECF and 44.1% (95% CI, 38% to 50%) with MCF (P =.692). Toxicity was tolerable, and there were only two toxic deaths. ECF resulted in more grade 3/4 neutropenia and grade 2 alopecia, but MCF caused more thrombocytopenia and plantar-palmar erythema. Median survival was 9.4 months with ECF and 8.7 months with MCF (P =.315); at 1 year, 40.2% (95% CI, 34% to 46%) of ECF and 32.7% (95% CI, 27% to 38%) of MCF patients were alive. Median failure-free survival was 7 months with both regimens. Global QOL scores were better with ECF at 3 and 6 months. CONCLUSION: This study confirms response, survival, and QOL benefits of ECF observed in a previous randomized study. The equivalent efficacy of MCF was demonstrated, but QOL was superior with ECF. ECF remains one of the reference treatments for advanced esophagogastric cancer.

Carcinoma-associated hemolytic-uremic syndrome: a complication of mitomycin C chemotherapy.

A thrombotic microangiopathy resembling the hemolytic uremic syndrome was diagnosed in 12 patients with adenocarcinoma, in whom the tumor was in complete or near-complete remission after treatment with mitomycin C-containing drug regimens. Microangiopathic hemolytic anemia, thrombocytopenia, and renal failure were initially present in all cases. All patients eventually developed pulmonary edema and systemic arterial hypertension, and three experienced neurologic complications. Blood transfusions exacerbated the syndrome in nine patients. High titers of platelet-aggregating plasma immune complexes were present in all six cases in which they were measured. The constituent antibody of each complex failed to react with mitomycin C antigen preparations, whereas in vitro reactivity to endodermally derived neoplasms was demonstrated. Plasmapheresis was associated with amelioration of the syndrome in only one patient. In patients receiving mitomycin C chemotherapy, the development of anemia and thrombocytopenia or azotemia may represent the initial manifestations of this newly defined thrombotic microangiopathy. A consistently effective form of management of this syndrome has not as yet been defined.

Mitomycin: ten years after approval for marketing.

Mitomycin was approved for marketing by the Food and Drug Administration in 1974 for use in gastric and pancreatic carcinomas when combined with other chemotherapeutic agents. Since then, mitomycin has been used extensively in combination chemotherapy for a variety of tumors, particularly in the past seven years. However, the contribution of this agent to the various drug regimens has not been adequately defined. Clear evidence of the drug's activity as a single agent has been seen in the intravesical treatment of superficial bladder carcinoma. Common toxicities include anorexia, vomiting, and myelosuppression. Less common, but potentially lethal, toxicities in the form of fibrosing alveolitis and microangiopathic hemolytic anemia with renal failure are being reported with increasing frequency. These potentially severe adverse effects, coupled with the still undefined role of mitomycin in systemic cancer chemotherapy, suggest that selection of this drug for other than investigational use should be made with care.

Cyclophosphamide versus 5-fluorouracil, doxorubicin, and mitomycin C (FAM') in the treatment of hormone-resistant metastatic carcinoma of the prostate: a preliminary report of a randomized trial.

There is no evidence that combination chemotherapy is superior to single agents in the treatment of advanced, hormone-resistant carcinoma of the prostate. We are reporting the preliminary results of a randomized trial comparing cyclophosphamide (CTX) with a combination of 5-fluorouracil, doxorubicin and mitomycin C (FAM'). Thirty-one patients were randomized and 30 of them were evaluable for response. Sixteen patients were treated with CTX and 14 with FAM'. On the CTX arm, eight (50%) of the patients had stable disease (SD) and eight (50%) had progressive disease (PD). On the FAM' arm, one (7%) patient had partial response (PR), five (36%) patients had SD and eight (57%) failed to respond. The difference in response rates between the two regimens was not significant (P greater than .72). The median time to progression (MTP) of all patients treated with CTX was six weeks and the MTP of patients treated with FAM' was 16 weeks (P less than .007). This difference in MTP could be explained in part by the unequal time to reevaluation between the two regimens. The MTP of the responders on CTX however, was 13 weeks, while for FAM' it was 33 weeks (P = .014). This difference suggests that FAM' has superior activity to CTX. Pain alleviation was seen in 25% of patients treated with CTX and in 64% of those treated with FAM' (P less than .01). Toxicity was tolerable on both regimens. We conclude that CTX and FAM' have similar response rates. Patients treated with FAM' enjoyed longer MTP and greater pain alleviation than those treated with CTX.

Long-term survivors in metastatic non-small-cell lung cancer: an Eastern Cooperative Oncology Group Study.

Between December 1979 and June 1983 the Eastern Cooperative Oncology Group (ECOG) treated 893 good-performance status patients with metastatic non-small-cell lung cancer (NSCLC) on one of seven phase III combination chemotherapies. The overall median survival was 23.5 weeks with no significant differences between treatments. One hundred sixty-eight patients (19%) survived greater than 1 year and 36 (4%) for greater than 2 years. The etoposide-platinum combination had the highest proportion of 1-year survivors (25%). Mitomycin-vinblastine-platinum (MVP), which had demonstrated the highest response rate, had significantly fewer 1-year survivors (12%) than any other regimen (P = .003). Analysis of pretreatment characteristics that distinguished patients who survived greater than 1 year from those who did not demonstrated that an initial performance status of 0, no bone metastases, female sex, no subcutaneous metastases, non-large-cell histology, less than 5% prior weight loss, no symptoms of shoulder or arm pain, and no liver metastases were predictors of longer survival. Of particular interest was the finding that response duration was significantly longer (P = .002) for those patients who experienced a longer time to best response. In addition, patients who survived greater than 1 year experienced greater degrees of nonlethal toxicity, in particular, gastrointestinal and hematologic, than patients who did not survive 1 year, (P = .006). A detailed chart review of 32 2-year survivors and 32 matched controls demonstrated that maintenance or improvement of performance status and maintenance of serum albumin levels at 3 months from the initiation of treatment were both important predictors of longer survival.

Feasibility study of combining metronidazole with chemotherapy.

Metronidazole, 1.5 g/sq m, was administered p.o. to patients with advanced malignancies 12 hr and 1 hr before and 6 hr and 24 hr after each of adriamycin, BCNU, and mitomycin-C. Doses of adriamycin varied from 50 to 90 mg/sq m. At an adriamycin dose of 75 mg/sq m, the median granulocyte nadir was 900/microliters and the median platelet nadir was 240,000/microliters. No enhancement of stomatitis or cardiotoxicity was noted at the doses studied. Doses of BCNU varied from 145 to 265 mg/sq m. At a BCNU dose of 240 mg/sq m, the median granulocyte nadir was 2600/microliters and the median platelet nadir was 102,000/microliters. Two patients developed hypotension that may have been due to a metronidazole-alcohol interaction. Doses of mitomycin-C varied from 10 to 20 mg/sq m. At a mitomycin-C dose of 20 mg/sq m, the median granulocyte nadir was 1300/microliters and the median platelet nadir was 81,000/microliters. Four of 40 patients developed pulmonary toxicity and one developed renal toxicity. Of 11 evaluable patients treated on the adriamycin regimen, 4 responded and 5 stabilized. With BCNU, 7 of 17 responded and 2 stabilized. With mitomycin-C, 2 of 32 responded and 12 stabilized. Overall, 4 of 8 patients with squamous cell carcinoma or adenocarcinoma of the lung attained partial remissions and one had a minor response. Using this metronidazole dose schedule, phase II studies are being conducted with adriamycin, 75 mg/sq m, in squamous cell and adenocarcinomas of the head and neck; with BCNU, 240 mg/sq m, in glioblastomas and squamous cell and adenocarcinoma of the lung; and with mitomycin-C, 20 mg/sq m, in adenocarcinomas of the breast and colon.

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.