Bleomycin, vincristine, mitomycin C and cis-platinum in gynecologic squamous cell carcinomas: A high incidence of pulmonary toxicity (original) (raw)
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Bleomycin pharmacology in relation to adverse effects and renal function in cervical cancer patients
Gynecologic Oncology, 1982
Clinical toxicity is related to bleomycin pharmacology and renal function in patients with advanced squamous carcinoma of the cervix. Adverse effects were more frequent in patients with severe renal impairment than in patients with adequate renal function. Pharmacokinetic data were obtained in four patients. This information suggests treatment guidelines for the use of bleomycin in patients with renal failure that may reduce the risk of excessive adverse effects. Bleomycin dose reduction of 75% and administration not more often than every 3 days may permit the use of this drug in patients with creatinine clearances of less than 25 ml/min in whom alternative chemotherapy with cis-platinum is not possible.
Assessment of bleomycin, adriamycin and mitomycin-C in the treatment of recurrent cervical cancer
BJOG: An International Journal of Obstetrics and Gynaecology, 1985
Twenty women with recurrent squamous cell carcinoma of the cervix were treated with bleomycin followed by adriamycin and mitomycin-C. Treatment was repeated every 28 days. In 18 patients who could be assessed there was one complete response and five partial responses (response rate 33%). Two partial responses were seen in 13 lesions arising from previously irradiated sites of disease (response rate 23%). Three complete responses and three partial responses were observed in 10 lesions arising from non-previously irradiated sites of disease (response rate 60%). In all responding cases tumour regression was noted before the end of the third cycle of treatment. Toxicity was predictable and manageable. These results suggest that chemotherapy may be used as a cytoreductive procedure before radical local treatment.
Annals of oncology : official journal of the European Society for Medical Oncology / ESMO, 2001
Three previous mitomycin-cisplatin-based chemotherapy trials conducted within the EORTC Gynecological Cancer Cooperative Group (GCCG) in patients with disseminated squamous-cell carcinoma of the uterine cervix (SCCUC) suggested that with such regimens a higher overall response rate and a higher complete response rate could be obtained compared to what might have been expected from cisplatin alone. In that respect the combination of bleomycin, vindesine (Eldesine), mitomycin C and cisplatin (BEMP) was the most promising. In the present study BEMP has been compared with the best single agent, cisplatin (P) in the expectation that improved response rates might translate into a better survival. Eligible patients were those with SCCUC and disseminated measurable disease outside previously irradiated areas, aged < or = 75 years, with a WHO performance status < or = 2 and adequate bone marrow, renal, hepatic and pulmonary function, who gave consent according to regulations followed i...
Medical and Pediatric Oncology, 1978
The incidence of pulmonary toxicities in 12 patients with prior exposure to bleomycin (BLM) was compared to the incidence of pulmonary toxicities in a matched group of 73 patients with stage III or IV testicular carcinomas treated with a regimen containing vinblastine, bleomycin, and cis‐diamminedichloroplatinum. The comparison demonstrates that prior exposure to bleomycin constitutes a significant risk factor and that the risk is additive; ie, prior doses should be added to current doses to determine the cumulative dose‐related probability of development of pulmonary toxicities.
Low dose bleomycin and methotrexate in cervical cancer
Cancer, 1976
Twenty patients with recurrent and disseminated carcinoma of the cervix were treated with Bleomycin, 10 mg/m2 weekly and Methotrexate, 10 mg/m? every fourth day. Twelve of the 20 (60%) had a greater than 50% shrinking of measured tumor masses lasting a median remission time of 7.5 months. The data suggest that combination protracted chemotherapy with these drugs of metastatic cervical cancer might improve the outlook of patients with this condition.
International Journal of Cancer, 2000
The purpose of this study was to determine the efficacy of mitomycin C as an adjunct to radiotherapy for the treatment of locally advanced cervix cancer. Patients with squamous-cell carcinoma of the cervix, stages IB2-IVA, were randomized to receive radiotherapy alone or radiotherapy with concomitant mitomycin C. An initial cohort of 160 patients, having a mean follow-up of 46 months, is analyzed. Intravenous mitomycin C, 15 mg/M 2 , was given on the first and sixth week of radiotherapy. The 78 patients in the radiotherapy with mitomycin C group and 82 patients in the radiotherapy alone group have a comparable distribution by age and stage (mean age 47 years; stage IB 3%, IIA 11%, IIB 48%, IIIA 1%, IIIB 36%, IVA 3%). The four-year actuarial survival rates for radiotherapy with mitomycin C and radiotherapy alone were 72% and 56%, respectively (P = 0.13). The four-year actuarial disease-free survival rates for radiotherapy with mitomycin C and radiotherapy alone were 71% and 44%, respectively, a statistically significant difference (P = 0.01). The four-year actuarial local recurrence-free survival rates for patients receiving radiotherapy with mitomycin C and radiotherapy alone were 78% and 63%, respectively (P = 0.11). Differences in four-year distant recurrence-free survival between radiotherapy plus mitomycin C and radiotherapy alone were significantly different at 85% vs. 61% (P = 0.01); this analysis is not adjusted for local failure. On subgroup analysis, stage III-IVA patients had a four-year actuarial disease-free survival of 75% for radiotherapy plus mitomycin C compared with 35% for radiotherapy alone (P = 0.03). There were no treatment-related deaths. Mild hematologic toxicity was seen only in the group treated with mitomycin C. No excess in non-hematologic toxicity has been observed thus far with combined mitomycin C and radiotherapy. In this open phase III trial of mitomycin C as an adjunct to radical radiotherapy for squamous-cell carcinoma of the cervix, there were Publication of the International Union Against Cancer minimal hematologic effects and no increase in acute radiation reactions. A statistically significant difference in favor of patients receiving mitomycin C is shown for disease-free survival. Thus far, there are trends in favor of those patients receiving mitomycin C for survival and local control. Patients with more advanced stage disease, predominantly stage IIIB, appear to have the most benefit. These preliminary results support the hypothesis that targeting hypoxic cells may lead to a therapeutic enhancement in the radiotherapy of cervix cancer. This trial continues to accrue patients and follow-up data.
Gynecologic Oncology, 1983
Thirty-five patients with advanced cervical cancer were treated with a combination chemotherapy regimen comprising cisplatin, vinblastine, and bleomycin (PVB). Sixty-six percent of 33 evaluable patients showed objective tumor response and complete remissions were seen in six (18%) patients. The median duration of tumor response in patients with recurrent cervical cancer was 24 weeks (range 8 to 104 weeks). Multivariate analysis of pretreatment variables including prior radiotherapy did not identify patients with a higher response probability. Nausea and vomiting were usual side effects of chemotherapy and there was one definite treatment-related death. Cervical cancer is responsive to cisplatinbased combination chemotherapy. The role of chemotherapy in conjunction with radiotherapy or surgery in the treatment of locally advanced cervical cancer remains to be defined.
Bleomycin lung toxicity: who are the patients with increased risk?
Pulmonary Pharmacology & Therapeutics, 2005
Bleomycin is an antibiotic drug with anticancer properties produced by Streptomyces verticillus [Cheson BD. The complex bleomycin-Fe has been the most studied because bleomycin joins the DNA and Fe at the same time, and release of free radicals happens in the presence of molecular oxygen [Hay J, Shahzeidi S, Laurent G. Mechanisms of bleomycin-induced lung damage. Arch Toxicol 1991;65:81-94].
European Journal of Cancer and Clinical Oncology, 1989
The long-term effects of bleomycin on pulmonary function were studied. Thirty-four patients with germ-cell cancer were followed for an average of 64 months (range 43-98 months). All had obtained complete remission during treatment and none had relapsed at the follow-up examination. Pulmonary function was tested by measurements of total lung capacity (TLC), vital capacity (VC), forced expiratory volume in one second (FEV1) and single breath diffusion capacity for carbon monoxide (TLCO). TLC and VC were significantly reduced by the treatment (P less than 0.05), but normalized during the follow-up. TLCO was initially reduced to a predicted median of 83%. In the smokers the initial TLCO was at a predicted median of 79%, while in non-smokers a median of 88% was predicted. During the first 2 months of treatment, TLCO increased both in smokers and non-smokers to predicted medians of 90% and 91%. Subsequently, however, a significant decrease to 72% was noted in the smokers, while the non-smokers had only an insignificant decrease to 84%. The decrease in TLCO was irreversible but not progressive. We conclude that bleomycin treatment is associated with a long-term sustained reduction in TLCO. The changes were most pronounced in the smokers.