Treatment of malignant nondysgerminomatous germ cell tumors of the ovary with vinblastine, bleomycin, and cisplatin

Fifteen patients with malignant nondysgerminomatous germ cell tumors of the ovary seen at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, were treated with a combination of vinblastine, bleomycin, and cisplatin (VBP). All patients underwent initial surgery: biopsy alone in one patient, unilateral salpingo-oophorectomy in ten patients, and bilateral salpingo-oophorectomy with or without hysterectomy in four patients. Seven patients received VBP as primary postoperative therapy. One patient died of progressive disease at 15 months following diagnosis. The other six patients are alive without evidence of disease 9 to 47 months from the time of diagnosis. Eight patients received VBP as second-line treatment; three patients had a complete response to therapy and are surviving disease-free 41 to 71 months from the time of diagnosis. Four patients treated secondarily had a partial response; three of these patients subsequently developed progressive disease and died, while one patient survived after undergoing salvage therapy with an etoposide-containing regimen. One patient had no discernible response to VBP therapy and died. The VBP regimen represents an aggressive, moderately toxic, short-term combination regimen that has promising activity against malignant germ cell tumors of the ovary.     

Combination chemotherapy with vinblastine, BCNU and cisplatin in advanced malignant melanoma

A combination chemotherapy including vinblastine (6 mg/m2 i.v. days 1-2), BCNU (100 mg/m2 i.v. day 3), and cisplatin (50 mg/m2 i.v. day 5) was given as salvage treatment in 46 consecutive, previously treated patients affected by metastatic malignant melanoma. Courses were planned every 4 weeks provided that a complete bone marrow recovery occurred, otherwise they were delayed for 1-2 additional weeks. Objective responses (3 CRs and 10 PRs) were observed in 13/46 (28%) patients; 12 cases had stable disease and 21 patients progressive disease during treatment. Median duration of response was 13 months (range, 5-18), and median survival was 11 months (range, 3-20) for all patients. Nausea and vomiting were the most distressing side effects, whereas a grade I leukopenia caused a delayed treatment in 90% of patients. In conclusion, the combination chemotherapy was moderately toxic and did not seem to give substantially better results than obtained with other reported regimens.     

Vinblastine, bleomycin, and cisplatin in malignant germ cell tumors of the ovary

Fourteen patients with malignant ovarian germ cell tumors were treated with vinblastine, bleomycin, and cisplatin. A complete clinical response was achieved in all 14 patients; however, 1 patient had small macroscopic disease present at second-look laparotomy. One patient died of bleomycin pulmonary toxicity. The remaining 13 patients are alive and free of disease from 20 months to 8 years and 8 months after initial diagnosis. Serum alpha-fetoprotein and beta-human chorionic gonadotropin levels were monitored in all patients and were found to be reliable indicators of response to treatment and disease status. The uninvolved ovary was preserved in seven patients without compromising the response to treatment, and one patient subsequently became pregnant. Vinblastine, bleomycin, and cisplatin chemotherapy appears to be a safe, effective combination and is recommended as the primary treatment of choice in the management of patients with malignant ovarian germ cell tumors.     

Severe vascular toxicity associated with vinblastine,bleomycin, and cisplatin chemotherapy

Summary Vascular toxicity following the use of vinblastine, bleomycin, and cisplatin (VBP) combination chemotherapy has been described. This report gives details of 5 patients who suffered acute life-threatening vascular events following such a chemotherapy regimen for germ cell tumors. In 3 of the cases no evidence of tumor was found at autopsy. Both an acute and a long-term vascular toxicity were seen. Large artery vascular disease may result from synergistic toxicity of the drugs comprising the regimen. These cases, with an additional 16 collected from the literature, suggest that major vascular disease is a significant side-effect of the VBP regimen.Supported by the Jazz and Blues Fund and by the Deborah Goldfine Reva Smilgoff Memorial Fund. Brian Samuels is the Triangle Industries Cancer Research Fellow     

Germ cell malignancies of the ovary: treatment with vinblastine, actinomycin D, bleomycin and cisplatin containing chemotherapy combinations

Seventeen patients with malignant ovarian germ cell tumors were treated with vinblastine, actinomycin D, bleomycin and cisplatin containing combinations. Many of these patients were heavily pretreated. Thirteen patients had objectively measurable disease and ten (77%) had an objective response (CR or PR). Four patients had nonmeasurable disease or were treated in an adjuvant setting and all remain without evidence of disease. Extensive disease and poor performance status were poor prognostic factors. Induction portions of these treatment programs which contained cisplatin appeared most effective. Maintenance portions without cisplatin appeared less effective.     

Treatment of malignant germ cell tumors of the ovary with bleomycin, etoposide, and cisplatin.

Since 1984, we have treated 26 patients with malignant ovarian germ cell tumors with a combination of bleomycin, etoposide (VP-16), and cisplatin (BEP) at The University of Texas MD Anderson Cancer Center (UTMDACC). The median age of the patients was 19 years (range, 8 to 32). All patients underwent initial surgery (unilateral salpingo-oophorectomy in 14, unilateral salpingo-oophorectomy plus abdominal hysterectomy in one, and bilateral salpingo-oophorectomy with or without hysterectomy in 11 patients). Twenty patients had no residual disease, three had less than or equal to 2 cm (one each, dysgerminoma, mixed, and immature teratoma), and three had more than 2 cm lesions (two dysgerminomas, one endodermal sinus tumor). Fourteen patients had pure dysgerminoma (five, stage I; one, stage II; six, stage III; and two, recurrent), and 12 had nondysgerminomatous tumors (five, stage I; two, stage II; three, stage III; and two, recurrent). All four patients with clinically measurable disease had a complete response. All four patients who underwent second-look laparotomy had negative findings. Twenty-five patients (96%) remain in sustained remission 10.4 to 54.4 months from the start of chemotherapy. One patient died of progressive disease 14 months after beginning chemotherapy. We conclude that the BEP regimen has excellent activity and acceptable toxicity in patients with malignant ovarian germ cell tumors.     

Combination chemotherapy of refractory lymphoma with cis-dichlorodiamineplatinum, vinblastine, and bleomycin

Therapy of advanced lymphomas after failure of chemotherapy with cytoxan and adriamycin containing combinations remains poor. We have treated 17 patients with refractory lymphomas of various histologies with an intensive regimen of cisplatin, vinblastine and bleomycin. These were three complete clinical responses (6, 10+, 8 months, respectively) and five partial responses (2.5, 3, 4, 7, 18 months, respectively) for a total of 8/17 responders. Four of the eight responders had bone or bone marrow involvement. In addition, three patients had dramatic shrinkage of measureable lesions, but the duration (less than 1 month) was too short to allow classification as a response. Toxicity included severe myelosuppression requiring that patients be hospitalized to the majority of cases, mild to moderate rise in serum creatinine levels in 41% of patients and one case of fatal pulmonary fibrosis. This regimen may be useful in patients with refractory or relapsing lymphoma; alternatively, it may be useful as part of an initial treatment protocol utilizing non-cross-resistant regimens for the management of patients with poor prognosis lymphomas.     

Modified cisplatin, etoposide (or vinblastine) and ifosfamide salvage therapy for male germ-cell tumors. Long-term results.

Between 1985 and 1989, 36 consecutive male patients with advanced germ-cell tumors, who had failed to be cured with either the cisplatin, vinblastine, bleomycin (PVB) or the cisplatin, etoposide, bleomycin (PEB) combinations, entered either of two modified salvage therapy regimens consisting of cisplatin, etoposide, and ifosfamide (PEI) or cisplatin, vinblastine and ifosfamide (PVI). All patients had evidence of active disease. Ifosfamide was given at the dosage of 2.5 gr/m2 (with mesna protection) on days 1 and 2; etoposide and cisplatin were given at the dosage of 100 mg/m2 and 40 mg/m2, respectively, on days 3 to 5. In the PVI schedule, vinblastine 6 mg/m2 was given on day 3. Overall, 20 (56%, C.I. 39 to 72) patients entered complete response (CR) or achieved disease-free status (NED) with post-chemotherapy surgery. After a follow-up of 2 to 7 years, 15 patients (42%, C.I. 24 to 58) remain alive and free of disease. None of the 9 patients unresponsive to the first-line therapy and/or with extragonadal primaries entered CR or achieved the NED status, versus 20 (74%, C.I. 58 to 91) of the 27 patients with primary testicular tumors who were responsive to the first-line therapy (p less than 0.001). PEI was used in 20 of these 27 patients, with excellent results (90% CR and 70% continuously NED) independently of primary therapy, PVB or PEB. By contrast, only 2 of the 7 patients treated with PVI following PEB entered CR. Toxicity was not life-threatening. Nine (25%) patients suffered granulocytopenic fever and 3 (8%) required platelet transfusions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combination bleomycin, ifosfamide, and cisplatin chemotherapy in cervical cancer

We report a phase II study of bleomycin, ifosfamide, and cisplatin (BIP) in cervical cancer. Our aims were to assess response rate, toxicity, and survival in women treated with this combination. Among 49 patients, 34 objective responses (69%) were seen, with 10 complete responses (20%). Toxic effects were assessed in 186 treatment cycles. All patients had alopecia and nausea and vomiting. Other effects included myelosuppression, infection, reduction in renal function, and disturbance of consciousness. These data indicate that BIP is highly active against advanced and recurrent cervical cancer.     

Combination chemotherapy of esophageal carcinoma using cisplatin, vindesine, and bleomycin

Sixty-one patients with epidermoid carcinoma of the esophagus have been treated with a three drug combination of cisplatin, vindesine, and bleomycin. Of 53 patients currently evaluable for response, 29 (55%) have had partial remissions: 7/16 with metastatic, and 22/37 with local-regional disease. The median duration of response in metastatic patients is eight months. Of 28 patients treated preoperatively, 23 (82%) had resectable disease. The major toxicities seen were nephrotoxicity and myelosuppression. Cisplatin, vindesine and bleomycin is an effective combination in the treatment of esophageal carcinoma. Effects on long-term survival cannot yet be evaluated.     

Combined chemotherapy with cisplatin and bleomycin for malignant tumor of the chest

Twenty-two patients with malignant chest tumor, mainly primary lung cancer, were given 73 courses of combined administration of cisplatin and bleomycin. The following results were obtained. Of 13 evaluable patients one CR and four PR, with an overall response rate of 38.5% were observed. Of seven patients who received 3 courses or more, four showed therapeutic effect, producing a response rate of 57.1%. CR was obtained in a patient with a relapse of malignant germ cell tumor showing positive HCG and AFP preoperatively. The patient survived for 445 days after the start of this treatment. Of nine patients with non-small cell lung cancer in whom therapeutic effect could be evaluated, three PR, four MR, and two PD with a response rate of 33.3% were obtained. Side effects due to cisplatin such as nausea, vomiting and impairment of renal function were all transient. Furthermore, myelosuppression caused by this chemotherapy was relatively mild compared with other chemotherapy regimens.     

Combination chemotherapy with vinblastine, bleomycin and methotrexate in DTIC-resistant metastatic melanoma.

Fifteen patients with metastatic DTIC-resistant malignant melanoma were treated with vinblastine, bleomycin and methotrexate combination chemotherapy. Three patients showed an objective response (one complete response). The therapy was well tolerated and easy to administer. This combination appears to produce in DTIC-resistance patients a response rate similar to that obtained with DTIC.     

Combination chemotherapy with cisplatin and bleomycin in esophageal cancer

Combination chemotherapy of cis-diammine dichloro platinum (II) (CDDP) and bleomycin was given to 10 patients with advanced squamous cell carcinoma of the esophagus. Nine patients had had major ablative surgical procedures, 8 had received prior radiotherapy, and 4 had been previously treated with chemotherapy. Responses were as follows (duration in months): 3 complete (1, 1.5, 7), 1 partial (1.5), and 3 minor. Vomiting related to CDDP was observed in 6 patients, and nephrotoxicity in 2 patients.     

Combination chemotherapy with vinblastine, bleomycin, and cis-diamminedichloroplatinum (II) in squamous cell carcinoma of the head and neck

Forty-five patients with advanced squamous cell carcinoma of the head and neck, 23 of whom had received no prior therapy, were given the combination of vinblastine, 4 mg/m2 intravenously (IV) on Day 1; bleomycin, 15 mg/day intramuscularly on Days 1-7; and cis-diamminedichloroplatinum (II), 60 mg/m2 with mannitol diuresis on Day 8. The regimen was repeated at three-week intervals, for a maximum of three cycles. Among the 23 patients without prior surgery or radiation, there were 5 complete responses and 12 partial responses, a 74% response rate; whereas, among the 22 with prior therapy, there were 2 complete responses and 8 partial responses, a response rate of 45%. Nineteen of 23 previously untreated patients were subsequently given radiation, 1 had surgery, and 1 had surgery plus radiation. Twelve of these 19 patients are currently free of disease, with a median duration of ten months from initial response. Four of the 22 previously treated patients received radiation and 2, surgery; 4 of these 6 patients are without evidence of disease. Renal dysfunction with elevation of serum creatinine occurred in 5 patients, a leukocyte count of less than 3,000/mm3 in 3, a platelet count of less than 100,000/mm3 in 2, skin changes in 11, hearing loss in 1, and both peripheral neuropathy and pulmonary changes in 1 patient. This combination of agents has substantial activity in untreated patients and may be useful as initial therapy in advanced head and neck malignancies by diminishing the incidence of local recurrence and distant metastasis.     

Combination chemotherapy with bleomycin,etoposide and cisplatin (BEP) for metastatic testicular teratoma: Long-term follow-up

127 men with previously untreated non-seminomatous germ cell tumours (NSGCT) of the testis were given BEP chemotherapy (bleomycin, etoposide and cisplatin) between 1979–1986. Long-term follow-up (median 65 months) has shown an overall 5 year survival of 87.2% (95% confidence limits 81.1%–93.3%). Outcome was related to both tumour volume and serum marker levels of alpha-fetoprotein (αFP) and beta human chorionic gonadotropin (HCG), with 5 year actuarial survivals of 97.8%, 72.2% and 26.7% respectively for small, large and very large volume disease defined by Medical Research Council criteria, and 91.2% and 60.8%, respectively, for men with low (αFP≤500 kU/l and HCG≤1000iU/l) or high serum marker levels. 79 men (62%) had a complete radiological and serum marker response to chemotherapy alone; residual masses postchemotherapy were resected in 39 patients (31%), showing undifferentiated tumour in only 6 (15%). 23 of the 127 patients (18%) failed to respond or developed recurrent disease after BEP; only 5 were successfully salvaged. Myelotoxicity of treatment was mild with grade 4 toxicity in 2% of chemotherapy courses and 3 episodes of neutropenic sepsis. Mean glomerular filtration rates fell by 15.6% between courses 1 and 4 of BEP. Bleomycin pneumonitis developed in 13% of cases with 1 fatality. So far 21 men have had children following chemotherapy, but semen analysis 12 months or more (median 36 months) after treatment showed azoospermia in 11 out of 54 (20%) men tested. BEP chemotherapy can be regarded as standard treatment for patients with metastatic NSGCT in low-risk categories, but more intensive therapy is required for advanced presentations. Strategies to develop “risk related” treatment are under investigation.     

Combination chemotherapy of MOPP-resistant Hodgkin's disease with adriamycin, bleomycin, dacarbazine and vinblastine (ABDV).

Twenty-four patients with advanced Hodgkin's disease, resistant to the MOPP regimen, were treated with a combination of Adriamycin, bleomycin, dacarbazine and vinblastine (ABDV). Fifteen (63%) achieved objective remission, 14 partial remissions and one complete remission. The median duration of remission in this group of patients was 6.5 months; four of the 15 patients are still in remission (8+, 8+, 9+, 10+ months). Objective remission occurred rapidly within 1.5 months. Regression was evident in disease within nodes, lung, liver and bone. Toxic manifestations caused by ABDV were well tolerated and reversible. In one patient death was directly attributed to drug toxicity. This combination has produced a better rate and duration of remission than that reported with single agent chemotherapy in MOPP-resistant patients with Hodgkin's disease. In our hands, ABDV did not equal the recent results reported with Bleomycin-CCNU-Velban in a seemingly similar group of patients.     

Good symptom relief with palliative MVP (mitomycin-C, vinblastine and cisplatin) chemotherapy in malignant mesothelioma

Purpose: To evaluate the therapeutic impact of a simple combination chemotherapy regimen on symptoms related to malignant mesothelioma.Materials and methods: Between October 1986 and June 1997, 39 patients with advanced inoperable malignant mesothelioma were treated with palliative MVP (mitomycin-C 8 mg/m² q. six weeks, vinblastine 6 mg/m² q. three weeks and cisplatin 50 mg/m² q. three weeks) chemotherapy and assessed for objective response and relief of symptoms.Results: Eight of 39 patients (20%) achieved an objective partial response with a median duration of nine months: only five patients had progression of disease during chemotherapy. Twenty-four of 39 (62%) had an overall improvement in their symptomology with particularly good responses for pain (79%). These benefits were independent of performance status. Resolution of symptoms was achieved in all responding patients within two treatment cycles. There was no statistically significant difference in duration and incidence of symptom response in those patients achieving radiological PR compared with those with no change and more than 60% of patients with radiological no change obtained useful symptom control. The treatment was well tolerated with only four patients developing grade 3 leucopenia and three with grade 3 nausea.Conclusions: MVP is a well tolerated regimen and its use in malignant mesothelioma provides useful symptomatic benefit. These results should be the basis for further trials of MVP in the management of mesothelioma with symptom control as a principal endpoint.     

Undifferentiated epithelial-rich invasive malignant thymoma: complete response to cisplatin, vinblastine, and bleomycin therapy

Two cases of complete remission plus one almost complete and another partial response of undifferentiated, invasive epithelial malignant thymoma using the combination of cisplatin, vinblastine, and bleomycin (PVB), are reported in four patients treated with this combination. Radiotherapy was instituted after completing the fourth course of chemotherapy in three patients. One patient died from intercurrent infection after the fourth cycle of combination chemotherapy. Three patients remain free of disease at the end of the treatment program. PVB appears to be highly active in this disease and deserves more extensive evaluation in multicenter clinical trials.     

Treatment of poor-risk germ-cell tumors with high-dose cisplatin and etoposide combined with bleomycin.

Seventy-two patients with far advanced ('high-risk') germ-cell tumors were treated with cisplatin 40 mg/m2 i.v. and etoposide 200 mg/m2 i.v. daily for 5 days and bleomycin 15 mg/m2 i.v. once a week. At least 3 cycles of this treatment were given at three-week intervals to all patients. Seventy-five percent of the patients obtained CR and 67% are without evidence of disease after a median observation time of 47 months (range 5 to 80 months). Hematologic toxicity was severe and 10% of the patients died due to treatment-related toxicity. Neurotoxicity was a clinical problem in 58% of the patients. Glomerular filtration rate decreased significantly after 3 cycles (29% +/- 16%). No clinically significant pulmonary toxicity was observed. The specific role of high-dose cisplatin in such intensive treatment has until now been the subject of only one randomized study in which no superiority of high-dose cisplatin was found. Significant improvement of therapeutic outcome over that of today's standard treatment conceivably necessitates an even greater increase in dose intensity of the active drugs--or inclusion of new drugs.     

Successful treatment of metastatic thymic carcinoma with cisplatin, vinblastine, bleomycin, and etoposide chemotherapy.

Thymic carcinomas are rare malignant neoplasms of the thymic epithelium that are distinguished from the malignant thymomas by the presence of cytologic atypia. Thymic carcinomas may metastasize outside of the thorax and are associated with a very poor prognosis. Complete responses of thymic carcinoma to chemotherapy alone have not been reported. A 21-year-old man with metastatic undifferentiated carcinoma of probable thymic origin is presented who achieved a pathologic complete response with cisplatin, vinblastine, and bleomycin chemotherapy. Additional consolidative chemotherapy with cisplatin and etoposide was administered. The patient remains disease-free 5 years after diagnosis. Cisplatin, vinblastine, and bleomycin chemotherapy appears to have significant activity against thymic carcinoma.