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PubMed1987

Chemotherapy for carcinomatous peritonitis and pleuritis with MMC-CH, mitomycin C adsorbed on activated carbon particles. Clinical trials.

A new drug dosage form comprising activated carbon particles adsorbing mitomycin C (MMC-CH) is designed to slowly release its components, and has affinity for the tumor surface and lymph nodes and a tendency to stay long in the local portion. The therapeutic index of MMC-CH in experimental carcinomatous peritonitis is 3.1 times as high as that of MMC-solution. In clinical experiments 81 patients with carcinomatous effusions were administered with MMC-CH (2.0-2.4 mg/kg in terms of MMC) in bolus intracavitarily. Fifty-one patients responded well to the MMC-CH therapy. Nineteen patients were alive for more than 6 months. The responders showed marked improvement in subjective symptoms, and 26 patients became dischargeable from hospital. Bone marrow suppression and peritoneal irritation were main adverse effects, but the symptoms were temporary and not so serious in spite of a high dose of MMC.

Charcoal↗
PubMed1987

Adjuvant perioperative hepatic arterial mitomycin C and floxuridine combined with surgical resection of metastatic colorectal cancer in the liver.

Twenty patients with colon cancer metastatic to the liver underwent successful hepatic resection and adjuvant perioperative therapy that included hepatic arterial mitomycin C and floxuridine (FUDR). The median survival for all 20 patients was 51 months: 10 are still alive with a median postoperative follow-up of 49 months; 6 are disease-free with a median postoperative follow-up of 43 months. Among 10 patients in whom the surgical margins of the specimen contained tumor cells, the median survival was 52 months. This survival was comparable to that among 10 patients in whom the surgical margins were tumor free (P = 0.22). Neither the number of metastatic liver deposits nor the disease-free interval between the primary diagnosis of colorectal carcinoma and the development of liver metastases significantly affected survival. A transient chemical hepatitis which resolved before the next scheduled treatment was associated with 50% of arterial chemotherapy cycles (approximately 70% of the patients). Gastric or duodenal ulcerations occurred in 23% of the patients. Surgical complications were either pulmonary such as pleural effusion or atelectasis, or wound infections and subphrenic abscesses. Although these results compare favorably with the results in previously published series, this aggressive adjuvant chemotherapy appears to be particularly justified in patients with tumor positive surgical margins or those with multiple tumor masses and, therefore, are characterized by a poor prognosis.

Adult↗
PubMed1987

Prospective study on the dose relationship of mitomycin C-induced interstitial pneumonitis.

Lung damage after mitomycin C (MMC) was first reported in 1978. Although this side effect has been frequently reported since then, there are no data on dose dependency nor on incidence. Therefore, the authors initiated a prospective study to obtain more data on this subject. Forty-four patients treated with MMC entered the study; 37 were evaluable. All patients were subjected to repeated physical examinations, chest x-rays, chest computed tomography (CT) scan and pulmonary function tests. The results were evaluated per cumulative dose level. None of the patients had clinical pulmonary toxicity develop; one patient had pulmonary changes on CT scan, the significance of which remained unclarified. The world literature on this subject was also reviewed. Based on the combined data of the present study as well as the literature review, the authors concluded that MMC-related lung toxicity is a dose-dependent side effect, occurring at cumulative dose levels of 20 mg/m2 or more. The incidence is likely to be less than 10%.

Adult↗
PubMed1987

5-Fluorouracil, doxorubicin, and mitomycin-C in the treatment of adenocarcinoma and large cell carcinoma of the lung.

Fifty-four patients with adenocarcinoma and large cell carcinoma of the lung, 16 with localized surgically resected disease and 38 with metastatic disease, were treated with 5-fluorouracil, doxorubicin, and mitomycin-C (FAM), in an attempt to prolong previously reported survival times in the patients. The postsurgical patients were given elective chemotherapy. Eighteen received radiation therapy for control of local disease. Tumor regression, attributable to chemotherapy alone, was noted in ten of 20 cases in whom there was measurable disease. The median survival time of all patients was 32 weeks, ranging from 25 weeks in those with distant metastases to 56 weeks in patients with surgically resected disease. FAM did not seem to produce any beneficial survival advantages.

Adenocarcinoma↗
PubMed1988

Prophylactic therapy for peritoneal recurrence of gastric cancer by continuous hyperthermic peritoneal perfusion with mitomycin C.

Continuous hyperthermic peritoneal perfusion (CHPP) with a solution that contains mitomycin C (CHPP-M) has been clinically introduced as a prophylactic treatment for peritoneal recurrence of gastric cancer with serosal invasion. Two studies, each with a treated and a control group, were performed. In the historical control study the postoperative 3-year survival rate of patients (73.7%) in the treated group (n = 38) was significantly higher than the survival rate (52.7%) of those in the control group (n = 55) (P less than 0.04). In the random control study the survival rate (83%) of patients in the treated group (n = 26) was also higher than that (67.3%) of those in the control group (n = 21) in the 30 months that followed gastric surgery. However, there was no significant difference. In the historical control study with respect to the postoperative complications, anastomotic leak was observed in 8.5% of patients who were given CHPP-M and 12.8% patients who did not have CHPP-M. In the random control study anastomotic leak was observed in 3.1% of patients who had CHPP-M and 7.1% of patients who did not have CHPP-M. The incidence of adhesive ileus in patients having CHPP-M did not increase in historical or random control groups. Postoperative prolonged intestinal paresis or chemical peritonitis were not induced by CHPP-M. These results indicate that CHPP-M is a simple, safe, and readily available prophylactic therapy for peritoneal recurrence that may follow gastric cancer surgery.

Adult↗
PubMed1988

Enhancement of cis-diamminedichloroplatinum and mitomycin C-induced sister chromatid exchanges by dibutyryl cyclic AMP in a human salivary gland adenocarcinoma cell line in culture.

A human salivary gland adenocarcinoma cell line was cultivated in the presence of dibutyryl cyclic AMP (dB-cAMP), cis-diammine dichloroplatinum (cisplatin) or mitomycin C (MMC) only, or of the combination of dB-cAMP and each of the antineoplastic drugs. Then the treated cells were examined for the induction of sister chromatid exchanges (SCEs), colony-forming efficiency (CFE) in semisolid agar medium and cell survival as measured by counting for viable cells. It has been found that the frequency of SCE induction is significantly increased by treatment of cells with cisplatin or MMC under the presence of dB-cAMP, when compared to that in the cells treated with cisplatin or MMC only. Moreover, marked reduction in CFE and cell survival was found to occur in the cells treated with the combination of dB-cAMP and cisplatin or MMC. These finding indicate that treatment of a human salivary gland adenocarcinoma cell line with dB-cAMP results in modification of SCE induction, CFE and cell survival in the cells exposed to cisplatin or MMC.

Adenocarcinoma↗
PubMed1988

Doxorubicin plus mitomycin C regimen in the prophylactic treatment of superficial bladder tumors.

Sixty patients with superficial papillary bladder cancer, Stages Ta and T1, received chemoprophylactic treatment to prevent recurrences after the complete resection of the primary lesion. The prophylactic regimen consisted of endovesical instillations alternating doxorubicin and mitomycin C. The first six instillations were given at weekly intervals. The remaining ten were given at monthly intervals beginning 4 weeks after the resection. At the mean follow-up time of 28 +/- 10 standard deviations (SD) months, 18 patients (30%) had a recurrence. Twelve of these 18 patients (20%) had a recurrence during treatment. The overall number of recurrences was 46 for a 100 patient-months recurrence rate of 2.72. Nine patients (15%) had a regression in stage and/or grade at the first recurrence, five (8.3%) had no change, and four (6.6%) had a worsening. At the first recurrence, the treatment was continued with augmented dosages of the same drugs. However, of 12 patients undergoing such second-line treatment, only two did not have further tumors. In three patients (5%), a subsequent muscle invasive tumor appeared. This two-drug treatment does not appear to be more effective than the usual one-drug prophylaxis. However, it does lead to an hypotheses about the chemosensitivity of the superficial tumors of the bladder and its correlation with the prognosis.

Adult↗
PubMed1988

Treatment of advanced non-small cell lung cancer with cisplatin, 5-fluorouracil, and mitomycin C.

Thirty patients with advanced non-small cell lung cancer (NSCLC) were treated with cisplatin (P), mitomycin C (M), and 5-fluorouracil (5-FU) chemotherapy. Twelve patients (40%) achieved major responses to therapy (11 partial, one regression). The median duration of partial response was 20 weeks. Median survival for the entire group was 29 weeks. Toxicity with this combination was moderate, with myelosuppression being the most significant toxic effect. Acute hematologic toxicity was generally mild, with 74% of patients having a leukocyte nadir greater than or equal to 2000/microliter and 67% with a platelet count nadir of greater than or equal to 100,000/microliter. There were, however, two toxic deaths during periods of treatment-induced cytopenia, 40% of patients developed significant anemia necessitating blood transfusions, and 33% had episodes of prolonged neutropenia. Nonhematologic toxicities were generally mild, although one patient developed a cardiac arrest of unclear etiology during day 4 of cycle 3 of treatment and died, for a total treatment mortality rate of 10% (three of 30). This drug combination produced a response rate comparable to those noted with other two or three drug cisplatin-based regimens in NSCLC but does not appear to offer any substantial advantage given its moderate toxicity, short duration of response, and necessity for substantial hospitalization.

Adult↗
PubMed1989

Cisplatin, 5-fluorouracil, mitomycin C, and concurrent radiation therapy with and without esophogectomy for esophageal carcinoma.

Twenty-nine patients with carcinoma of the esophagus were treated with 5-fluorouracil (5-FU) (1000 mg/m2/d as a continuous intravenous [IV]infusion on days 1 through 4), cisplatin (100 mg/m2 IV on day 1), mitomycin C (10 mg/m2 IV on day 1), and concurrent radiation therapy (4500 cGy/4.5 wk). If no disease progression was observed, operable patients underwent surgery 4 to 6 weeks after completion of radiation therapy. A thoracotomy with a gastric pull-through operation was performed in the first six patients. Subsequently, a transhiatal ("blunt") esophagectomy was used. Twenty-five patients had squamous cell histology and four had adenocarcinoma. Of 25 patients with squamous cell carcinoma, 13 underwent esophagectomy. The clinical complete response rate was 61% (eight of 13 patients), with a pathologic complete remission documented in five of 13 patients (38%). The overall local tumor sterilization rate was 53% (seven of 13 patients). In the 12 patients who did not undergo surgery after chemoradiotherapy, four had a complete clinical response (33%) and five had a partial response (41%). Symptoms or signs of local disease recurrence or stricture were noticed in ten of 12 patients who did not undergo surgery (83%), compared with 28% of patients who underwent surgery. The median survival time of the group receiving surgery was 10 months, compared with 5 months for those who did not undergo operation (P = 0.027). Patients undergoing transhiatal esophagectomy had shorter postoperative hospital stays and fewer serious complications, compared with patients undergoing transthoracic esophagectomy. The use of chemoradiotherapy and transhiatal esophagectomy for esophageal carcinoma should be evaluated using alternative sequences of treatment (e.g., postoperative therapy) to reduce toxicity while maintaining local control of disease.

Adenocarcinoma↗
PubMed1989

Mitomycin C adjuvant chemotherapy after Wertheim's hysterectomy for stage IB cervical cancer.

Patients undergoing radical surgical treatment for Stage IB and IIA cervical carcinoma are at high risk of developing local recurrence and/or distant metastases when one or more of the following factors are present: presence of metastatic pelvic lymph nodes, a large primary growth, full-thickness tumor invasion of the cervix, clinically undetected parametrial extension, and lymphatic/vascular channel permeation in the cervix by tumor cells. Carcinoma of the cervix appears to be behaving like a systemic disease. Therefore, systemic measures should be considered in its therapy. The authors report the initial experience with the use of mitomycin C as a single agent adjuvant in 16 patients with Stage IB carcinoma of the cervix who had undergone Wertheim radical hysterectomy and were thought to be in this high-risk group. Fourteen of the patients are alive and free of disease after durations of follow-up ranging from 16 to 38 months, the disease-free survival at a median follow-up of 29 months being 87.5%. One patient required discontinuation of adjuvant chemotherapy because of severe marrow toxicity; however, in view of the presence of a multiple risk factors, pelvic irradiation was given instead. She died 13 months later from disseminated disease. A second patient died 6 months later from congestive cardiac failure.

Adenocarcinoma↗
PubMed1989

Intrahepatic mitomycin C as a salvage treatment for patients with hepatic metastases from colorectal carcinoma.

Sixty-four evaluable patients with hepatic metastases from colorectal carcinoma, who did not have evidence of extrahepatic disease, were treated with intrahepatic (IH) mitomycin C (M) after disease progression or intolerance to treatment with IH fluorodeoxyuridine (FUDR). Eleven patients (17%) had a partial response (PR) to IH M and ten (16%) patients had stable disease. Patients who responded to IH FUDR were more likely to respond to IH M when compared with those who progressed on IH FUDR (47% versus 13%, respectively; P = 0.013). Those who were switched to IH M because of hepatotoxicity on IH FUDR also were more likely to respond to IH M than those who were switched because of progression on IH FUDR (75% versus 27%, respectively; P = 0.022). Baseline laboratory values, the percent of tumorous liver involvement, prior history of systemic chemotherapy, and the interval from diagnosis to initiation of IH M did not help predict response. Toxicity was mild and well tolerated. The overall median survival time of the 64 evaluable patients was 9.0 months from the start of IH M therapy. We conclude that IH M has some salvage benefit in patients with hepatic metastases.

Colorectal Neoplasms↗
PubMed1990

Histologic changes induced by intraperitoneal chemotherapy with 5-fluorouracil and mitomycin C in patients with peritoneal carcinomatosis from cystadenocarcinoma of the colon or appendix.

Intraperitoneal chemotherapy with mitomycin C and 5-fluorouracil has been used to rescue patients from peritoneal carcinomatosis after perforated cystadenocarcinoma of the large bowel or appendix. A staging celiotomy was used to asses the results of therapy. In nine patients tumor was recovered from the abdominal cavity and was subjected to careful histopathologic examination. The posttreatment appearance of the tumor was compared with that before treatment. Also, tumor deposits harvested from these same patients, but from anatomic sites not directly exposed to chemotherapy were examined. The most striking findings observed in treated patients were as follows: (1) the marked reduction in the number of foci of atypical neoplastic epithelium lining the mucin globules, and (2) atrophy and degeneration of the atypical neoplastic epithelium. All treated patients showed these effects but they were not in all sampled tumor specimens, suggesting nonuniform drug distribution in the abdominal cavity and limited penetration of chemotherapy into tumor. The authors conclude that intraperitoneal chemotherapy produces marked histologic changes in mucinous tumors when there is direct contact between tumor and intracavitary drugs.

Adult↗
PubMed1990

A phase II trial of 5-fluorouracil, doxorubicin, mitomycin C, and leucovorin in advanced gastric carcinoma.

To determine the feasibility and toxicity of combining leucovorin (CF) with a 5-fluorouracil (5-FU) combination chemotherapy regimen currently accepted by many as standard treatment for gastric cancer, CF (500 mg/m2) was administered in combination with the Georgetown 5-FU, doxorubicin, and mitomycin C (FAM) regimen. Thirty-two patients with advanced adenocarcinoma of the stomach were evaluable for toxicity and 26 patients with measurable disease were evaluable for response. Fifty-four percent of patients were previously treated with chemotherapy or radiation therapy. The response rate was 38% (95% confidence interval, 21% to 59%). The median duration of response was 6 months (range, 2 to 23+ months). The estimated median survival time was 6.8 months for patients with measurable disease and 11.5 months for all 32 patients. Although diarrhea is dose limiting when 5-FU and CF are administered weekly for 6 of 8 weeks, diarrhea occurred rarely on this combination regimen with 5-FU and CF administered only 4 of every 8 weeks. The dose-limiting toxicity of FAM-CF was cumulative myelosuppression, which also occurs with the standard FAM regimen. As a result, the administered dose intensity of 5-FU decreased as patients continued on study. Thus, a randomized comparison of FAM with FAM-CF would not determine whether CF modulation increases the efficacy of 5-FU when it is administered in optimal doses to patients with gastric cancer.

Adult↗
PubMed1983

Sister chromatid exchanges and chromosomal aberrations induced by mitomycin C in mouse lymphocytes carrying a leukemogenic virus.

The induction of chromosomal damage (sister chromatid exchanges (SCEs), chromosomal aberrations, and micronuclei) in T lymphocytes from mouse spleen was analyzed after treatment in vivo with different concentrations of mitomycin C (MMC). Lymphocytes were derived from BALB/Mo mice, which carry an endogenous type C retrovirus (Moloney murine leukemia virus, M-MuLV), and from BALB/c mice (controls, M-MuLV-free). Chromosomal damage was determined in vitro on lymphocytes stimulated with concanavalin A (Con A) and incubated for two generation cycles with bromodeoxyuridine (BUdR). The baseline frequency of SCEs was significantly higher in untreated BALB/Mo than in BALB/c lymphocytes. The frequencies of SCEs were significantly increased by increasing doses of MMC in both BALB/c and BALB/Mo T lymphocytes. Treatment with a low dose of MMC (0.3 mg/kg) produced an additive effect on SCE frequency in BALB/Mo lymphocytes, which was gradually suppressed by increasing the MMC concentration (3-5 mg/kg). Indeed, the levels of SCEs became significantly lower in BALB/Mo than in BALB/c lymphocytes at the highest MMC concentration tested (10 mg/kg), indicating that a negative synergistic effect was eventually produced. Chromosomal aberrations (breaks and total aberrations) were significantly increased by the highest MMC doses (5-10 mg/kg) and were more frequent in BALB/Mo than in BALB/c lymphocytes at 10 mg/kg MMC. The frequencies of micronuclei were increased by all MMC doses and were significantly higher in BALB/Mo than in BALB/c lymphocytes at 10 mg/kg MMC. These results are referred to interferences of M-MuLV and MMC with the function of enzymes, such as DNA topoisomerases, involved in the mechanism of SCE production.

Animals↗
PubMed1990

Investigation of plasma von Willebrand factor and circulating platelet aggregating activity in mitomycin C-related hemolytic-uremic syndrome.

We have studied the ability of the plasma to induce aggregation of both homologous and heterologous platelets in four patients with hemolytic-uremic syndrome (HUS) associated with chemotherapy with mitomycin C (MMC). Neither platelet aggregation was elicited by patients' plasmas nor the in vitro addition of purified von Willebrand factor (vWF) had any effect on the aggregation pattern. In addition, ristocetin-induced binding of patients' vWF to formaldehyde-fixed platelets was normal, and multimeric vWF analysis revealed a normal structure of patients' plasmatic vWF whatever the clinical stage in which it was studied. These findings suggest that, in spite of the existence of common clinical and biological features in the various forms of HUS, the pathogenesis of MMC-related HUS may be, at least in part, different from that of the other forms of HUS in which both platelet-aggregating activity and alterations in the vWF are found.

Blood Platelets↗
PubMed1991

[The effect of the vasoconstrictor glycylpressin on the bioavailability of mitomycin C].

During an intra-arterial chemotherapy of patients with liver metastases the plasma concentration-time curves of Mitomycin C (1) after occlusion of the common hepatic artery by the vasoconstricting agent Glycylpressin (2) were investigated. Vasoconstriction by 2 leads to significantly (p less than 0.01) lower blood levels of 1 in contrast to bolus injection of 1 without 2 under identical dosage regimens. This reduction of systemic availability of about 50% leads to a corresponding higher availability for the tumor region.

Aged↗
PubMed1984

Advanced gastric cancer: experience in Scotland using 5-fluorouracil, adriamycin and mitomycin-C.

Eighty-four patients with advanced gastric cancer treated in four centres in Scotland between June 1980 and December 1982 were reviewed following treatment with 5-fluorouracil, adriamycin and mitomycin-C (FAM). Eighty-one patients were evaluable. Twenty-eight patients (35 per cent) responded (four complete) with a median duration of response of 10.5 months and median survival of 17 months. Ten are still alive. Response was associated with an improvement in performance status. Eight patients (10 per cent) had stable disease with a median survival of 10 months. Forty-five (55 per cent) had progressive disease with a median survival of 4.5 months; one patient remains alive. Analysis of prognostic variables indicated that the presence of hepatic metastases had a negative influence on response to FAM (P less than 0.001). Treatment was well tolerated on an outpatient basis. FAM offers good palliative therapy in a proportion of patients with this disease, especially those without overt liver metastases.

Adenocarcinoma↗
PubMed1982

Flow cytometric characterization of the response of Fanconi's anemia cells to mitomycin C treatment.

DNA flow histogram analysis, using 33342 Hoechst as a stain, has been used to detect the effect of the potentially bifunctional alkylating agent, mitomycin C (MMC) on dermal fibroblasts from patients with Fanconi's anemia (FA), a hereditary human disease characterized by pancytopenia, hypersensitivity to DNA-crosslinking agents, congenital abnormalities and a predisposition for neoplasia. At 24 or 48 hr after a 2-hr exposure to 0.05 or 0.10 micrograms/ml MMC, (3)HdT incorporation was reduced to a greater extent in FA cells than in normal cells. Cells sorted from the last half of S phase showed a slightly greater inhibition of (3)HdT incorporation than did those sorted from the first half of S. Fanconi's anemia cells exhibited a marked accumulation in the G(2) + M peak of flow histograms following exposure to MMC. Twenty-four hr after treatment with .0.5 micrograms/ml MMC, the G(2) + M fraction of FA cells (eight lines) increased to more than 0.5 from a control value of approximately 0.02. Both normals (six lines) and heterozygotes (eight lines) showed, on the average, much less of a G(2) + M increment than did FA cells, even after exposure to 0.1 micrograms/ml MMC. Examination of cells sorted from the G(2) + M peak revealed that MMC-treated FA cells were blocked prior to mitosis. To determine whether the response of FA cells was specific for bifunctional alkylating agent, cells were also treated with ethylmethanesulfonate, a monofunctional agent. Twenty-four hours after exposure to 0.25 or 0.5 mg/ml ethylmethanesulfonate, FA and normal cells showed similar, small increases in the G(2) + M peak. The results suggest the utility of flow cytometry in the diagnostic evaluation of fibroblasts from patients suspected of having Fanconi's anemia.

Alkylating Agents↗