Adjuvant vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum chemotherapy regimen with and without maintenance in patients with resected stage IIB testis cancer

A total of 42 patients with stage IIB nonseminomatous germ cell tumors of the testis after orchiectomy and retroperitoneal lymph node dissection received adjuvant chemotherapy with the modified vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum regimen. Of the patients 29 had N2B and 13 had N3 nodal categories. Adjuvant vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum chemotherapy was given with maintenance in the first 24 patients and without maintenance (2 months of chemotherapy) in the subsequent 18. Chemotherapy with maintenance was given for 1 year and began with 2 inductions 3 to 4 weeks apart: 600 mg./m.2 intravenous cyclophosphamide, 30 mg. intravenous bleomycin, 1 mg./m.2 intravenous actinomycin D and 4 mg./m.2 intravenous vinblastine on day 1, 20 mg./m.2 bleomycin daily by continuous 24-hour induction on days 1 to 3 and 120 mg./m.2 intravenous cis-platinum with mannitol-induced diuresis on day 4. Maintenance with 6 mg./m.2 intravenous vinblastine and 1 mg./m.2 intravenous actinomycin D every 3 weeks was initiated 3 weeks after the second induction for the remainder of the year. Adjuvant vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum chemotherapy without maintenance was given for 2 months and used 3 inductions identical to those described previously. Complete remission has been maintained in 41 of 42 patients: all 24 who received maintenance chemotherapy and 17 of 18 who did not. One patient had a relapse with sarcoma and 6 required broad-spectrum antibiotics for fever during myelosuppression. A temporary increase in the serum creatinine of more than 2 mg. per cent occurred in 1 patient. Chronic renal failure or pulmonary fibrosis was not seen. Our results show that vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum chemotherapy is effective in the prevention of recurrences in patients with resected stage IIB disease, and suggest that adjuvant chemotherapy is equally effective with or without maintenance.     

Vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum combination chemotherapy in metastatic testis cancer--a 1-year program

Vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum were given in 31 men with stage III or bulky stage II malignant germ cell tumors of the testis and no previous chemotherapy, 25 of whom were evaluable. This regimen was given for 1 year and began with 3 successive inductions at 3 to 4-week intervals: 600 mg./m.2 intravenous cyclophosphamide, 4 mg./m.2 intravenous vinblastine, 30 mg. intravenous bleomycin and 1 mg./m.2 intravenous actinomycin D on day 1, followed by continuous 24-hour infusion of 20 mg./m.2 bleomycin per day on days 1 to 3 and 120 mg./m.2 intravenous cis-platinum with mannitol-enhanced diuresis on day 4. Any residual disease was resected 1 month after the third induction. If the resected specimen contained malignant tissue an additional 2 inductions (total 5) were given before brief maintenance with 6 mg./m.2 intravenous vinblastine and 1 mg./m.2 intravenous actinomycin D every 3 weeks for the remainder of 1 year. Complete remission occurred in 23 of 25 evaluable patients (92 per cent) and 20 (80 per cent) remain free of disease with a median followup of more than 27 months. Patients with minimal metastatic deposits and those without teratoma in the testis tumor had high complete remission rates with chemotherapy alone. Patients with advanced disease and with teratoma in the primary tumor benefited more frequently from the combined approach. Myelosuppression was the major potentially serious toxic effect. Vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum were superior to prior vinblastine, actinomycin D and bleomycin programs because higher complete remission rates were achieved with shorter duration of treatment and lesser disability.     

Treatment of recurrent and widespread testicular tumor by radical reductive surgery and multiple sequential chemotherapy.

There were 37 patients with stages II and III testicular tumors treated by a combination of multisequential chemotherapy and radical reductive surgery. Two protocols were used: 30 patients received bleomycin, vinblastine, platinum, doxorubicin hydrochloride, cyclophosphamide and actinomycin D (protocol A), and 7 patients received bleomycin, vinblastine, vincristine, platinum and actinomycin D (protocol B). A complete clinical remission was achieved in 19 of the 37 patients (51.3 per cent), for an average survival of 12.9 months to date. A partial clinical remission was obtained in 7 patients (18.9 per cent), for an average survival of 14.2 months. Eleven of the patients (29.7 per cent) escaped from therapeutic control. The collective response (complete and partial clinical remissions) represented 70.2 per cent of the patients (26 of 37), with an average survival of 14.8 months. A new approach for the simultaneous excision of metastases in the abdomen and the chest is described and the rational basis for the combination treatment of these tumors is discussed.     

Treatment of previously untreated (by hormonal manipulation) stage D adenocarcinoma of prostate with combined orchiectomy,estrogen, and cis diamminedichloroplatinum

Thirty-four patients with Stage D adenocarcinoma of the prostate previously untreated by hormonal manipulation were treated with the combination of orchiectomy, estrogen therapy, and infusion of cis diamminedichloroplatinum (1 mg./Kg./week) for six weeks initially and every three weeks thereafter. A partial objective response was observed in 22 of 34 patients (64.7 per cent). This response lasted three to twenty-nine months, with an average of 9.3 months. Five patients (14.7 per cent) had a significant decrease or disappearance of bone pain and became ambulatory. Six patients (17.6 per cent) remained stable. One patient (2.9 per cent) did not respond to treatment and showed progression of his disease. The toxicity of the treatment was mild to moderate. Most of the patients were treated in the outpatient department. The combination of cis platinum, orchiectomy, and estrogen therapy appears to be the most effective method of treatment for previously untreated (by hormonal manipulation) Stage D adenocarcinoma of the prostate.     

Treatment of estrogen-resistant stage D carcinoma of prostate with cis diamminedichloroplatinum.

Forty-five patients with rapidly progressive, estrogen-resistant Stage D adenocarcinoma of the prostate were treated with infusions of cis diamminedichloroplatinum (cis platinum) (1 mg./Kg./week) for six weeks initially and every three weeks thereafter. A partial objective response was observed in 13 of 45 patients (29 per cent). This response lasted from two to sixteen months with an average of six months. Eighteen patients (40 per cent) had a significant decrease or disappearance of bone pain and became ambulatory. Six patients (13 per cent) remained stable, and 8 patients (18 per cent) did not respond to treatment and showed progression of their disease. The toxicity of the treatment was mild to moderate. Most of the patients were treated in the outpatient department. Cis platinum appears to be the most effective drug available to date for the treatment of advanced carcinoma of the prostate.     

Vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum for advanced germ cell testis tumors: Brazilian experience

Disseminated germ cell testicular cancer proved to be highly sensitive to platinum-containing chemotherapy regimens. We present data concerning the treatment of advanced seminoma and nonseminomatous tumors in a developing country. We treated 30 patients with advanced germ cell testis tumors with 3 or 4 cycles of vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum. Surgical resection of residual masses was done 30 days after completion of chemotherapy in 18 patients. The histology of the primary tumor was seminoma in 13 patients and nonseminomatous tumors in 17. Toxicity was mild and no treatment-related deaths occurred. All 13 patients (100 per cent) with seminoma and 12 of 17 patients (71 per cent) with nonseminomatous tumors had a complete response to chemotherapy, and 1 of 17 patients was free of disease after a debulking operation and additional chemotherapy. A total of 3 patients with seminoma and 2 with nonseminomatous tumors had recurrences 5 to 8 months after an initial complete response and received additional chemotherapy (VP-16 regimen) with or without radiotherapy. Complete clinical response was achieved in 4 of 5 patients. Median followup was 24 months (range 8 to 38 months) in the 13 patients with seminoma and 28 months (range 9 to 58 months) in those with nonseminomatous tumors, and 13 (100 per cent) and 12 (71 per cent), respectively, are alive without evidence of disease. These data suggest that the protocol of vinblastine, actinomycin D, bleomycin, cyclophosphamide and cis-platinum is highly effective and minimally toxic in the treatment of disseminated germ cell testicular cancer, inducing an 83 per cent long-lasting clinical remission. Seminomas seem to be equally or even more sensitive than nonseminomatous tumors to this platinum-containing chemotherapy regimen. Recurrence after initial complete response can be treated successfully with regimens containing VP-16.     

Chemotherapy for disseminated testicular cancer.

Fifty patients with disseminated testicular cancer were treated with a three-drug combination consisting of cis-diaminedichloroplatinum, vinblastine, and bleomycin. Three patients were considered unevaluable due to early death. This chemotherapy regimen produced 74 per cent complete and 26 per cent partial remissions. Furthermore, five patients in partial remission became disease-free following the surgical removal of residual disease, producing an overall 85 per cent disease-free status. Toxicity, although significant during remission induction with cis-platinum, vinblastine, and bleomycin, was usually manageable. Maintenance therapy with vinblastine and BCG was very well tolerated, and only two patients in complete remission have experienced a relapse on maintenance therapy, one of whom had a central nervous system relapse. Thirty eight of these patients remain alive, and 32 remain alive and disease-free 6+ to 30+ months. We feel that this regimen represents a major advance in the management of patients with disseminated testicular cancer.     

Adjuvant chemotherapy in non-seminomatous testis cancer: "mini-VAB" regimen: long-term followup

Since 40 to 50 per cent (range 20 to 80 per cent) of patients with stage II non-seminomatous germ cell tumors of the testis suffer relapse after orchiectomy and retroperitoneal lymph node dissection, relatively non-toxic adjuvant chemotherapy (consisting of vinblastine, actinomycin D, bleomycin and chlorambucil) was given to 62 patients after lymphadenectomy. Of these patients 82 per cent remained free of disease with a 4-year median followup and 18 per cent had relapse. Retrospective analysis reveals that no patient (0 of 33) with stage IIA and 38 per cent (11 of 29) with stage IIB disease had relapse. Patients with histologic evidence of extranodal extension of disease (N3 category) had the highest relapse rate (62 per cent). Based on our experience we recommend that patients with resected stage IIB disease, particularly those with extranodal extension of tumor, receive aggressive adjuvant chemotherapy.     

Treatment of advanced carcinoma of the prostate (stage D) with infusion of cis-diamminedichloroplatinum (II NSC 119875): a pilot study

A study was done on 21 patients who had advanced carcinoma of the prostate (stage D) treated with 1 mg./kg. cis-diamminedichloroplatinum per week for 6 weeks. The infusions were then spaced every 3 weeks thereafter. One patient had never been treated previously and 20 patients were failures of previous therapy with estrogens and/or radiotherapy and/or chemotherapy. A partial objective clinical remission was seen in 9 of the 21 patients (43 per cent). This response lasted from 3 to 14 months, with an average of 5.8 months. The responses were evidenced by a 50 per cent or more decrease of lesions in the liver (2 patients), recalcification of a bone lytic lesion (1 patient), disappearance of positive lymph nodes in the neck (2 patients), disappearance of pleural effusion (1 patient), disappearance of lymphatic block of lower extremities (2 patients) and disappearance of lung metastases and ureteral obstruction (1 patient). Six patients (28.5 per cent) had a complete disappearance of the bone pain and became ambulatory and asymptomatic, 2 patients (9.5 per cent) with bony metastases remained asymptomatic and apparently stable and 4 patients did not respond to treatment and showed progression. Cis-diamminedichloroplatinum seems to be the most effective drug available to date for the treatment of advanced carcinoma of the prostate.     

Improved chemotherapy in disseminated testicular cancer.

Two combination chemotherapy regimens for disseminated testicular cancer are described. Our present regimen of platinum vinblastine and bleomycin has been highly successful, producing 16 complete (80 per cent) and 4 partial (20 per cent) remissions. Furthermore, 2 patients have been rendered free of disease by the surgical removal of residual disease, making the effective complete remission rate in these 20 patients 90 per cent. Of these patients 16 are alive and 14 are free of disease for more than 8 to more than 20 months. Despite the significant toxicity during the first 12 weeks of this therapeutic regimen it usually was manageable and maintenance therapy produced minimal toxicity. We believe that this regimen is a major advance in the management of patients with disseminated testicular cancer.     

Comparative study of risk criteria for germ cell tumor]

The development of cisplatin-based chemotherapy has achieved a high cure rate in patients with advanced germ cell tumors (GCT) and it is more important to predict the prognosis of each patient before treatment and select the most suitable regimen of therapy. To date, 4 risk criteria for GCT are presented. From November, 1985 to April, 1991 our treatment protocol for GCT consisted of VAB-6 (vinblastine, actinomycin D, bleomycin, cisplatinum) or PVeBV (vinblastine, etoposide, bleomycin, high-dose cisplatin) as the induction chemotherapy and VIP (etoposide, ifosfamide, cisplatin) as the salvage chemotherapy. In total, 12 patients were entered on this protocol. They were divided into 2 groups based on the actual clinical course. Those who achieved complete remission within 3 cycles of chemotherapy were divided into "good response group" and others were into "poor response group". These results were compared with those classified by the 4 risk criteria. As a result of our study "The Indiana Staging System" seemed to be the most useful.     

Preliminary results of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for transitional cell carcinoma of the urothelium

The M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) regimen was used to treat 25 patients with transitional cell carcinoma of the urothelial tract. Treatment consisted of monthly cycles of 30 mg. per m.2 methotrexate, followed 24 hours later by 3 mg. per m.2 vinblastine, 30 mg. per m.2 doxorubicin and 70 mg. per m.2 cisplatin, and concluded with repeat vinblastine and methotrexate on days 15 and 22. Significant tumor regression was noted in 71 per cent of the patients. Complete clinical remission was observed in 12 of 24 patients (50 per cent, 95 per cent confidence limits 30 to 70 per cent) with bidimensionally measurable indicator lesions, 6 of whom had pathological confirmation. After surgical exploration 4 patients required downstaging to a partial remission. The median duration of response has not yet been reached at 9.5 plus months, range 4.5 plus to 16 plus. Five patients (21 per cent) had a partial clinical remission for 4 to 8 plus months, 1 had a minor response for 4 months and 1 had stable disease for 11 months. All metastatic sites responded, including bone (6 of 8 cases), liver (3 of 5), locoregional (12 of 17) and intravesical (6 of 7) disease. Toxicity included moderately severe myelosuppression that resulted in nadir sepsis in 4 patients and a drug-related death in 1, mild to moderate anorexia, vomiting, alopecia and renal dysfunction. These preliminary results suggest that treatment with methotrexate, vinblastine, doxorubicin and cisplatin is extremely effective against locoregional and disseminated urothelial tract tumors, with the expectation (95 per cent confidence limits) of inducing objective tumor regression in 53 to 89 per cent of the cases.     

VAB-6 combination chemotherapy in patients with stage II, III testicular tumor

Between 1983 and 1985, six patients with advanced testicular cancer were treated with 3 cycles of vinblastine, actinomycin D, bleomycin, cyclophosphamide and cisplatinum (VAB-6 combination chemotherapy without maintenance). The histology of the primary tumor was seminoma in one patient and nonseminomatous germ cell testicular tumor (NSGCTT) in 5. Five men with stage III or bulky stage II diseases received no prior chemotherapy but one had received another chemotherapy without cisplatinum. Two patients showed a complete response to chemotherapy. Three were partial responders free of disease after a debulking operation and additional chemotherapy. The other patient who had NSGCTT had recurrence 5 months after the last induction chemotherapy and received additional chemotherapy (PVeBV regimen). Median follow-up was 16 months (range 2 to 28 months) and all patients are alive with no evidence of disease. Severe myelosuppression and serious renal toxicity were not experienced. Marked, but transient elevation of serum transaminase were observed in all patients. These data suggest that this protocol is highly effective and minimally toxic in the treatment of disseminated testicular tumor.     

New preoperative chemotherapy for bladder cancer using combination hemodialysis and direct hemoperfusion: preliminary report

Preoperative chemotherapy and subsequent cystectomy were performed on 11 patients with locally invasive bladder cancer. Three chemotherapy regimens were tested: 1) 2 to 3 mg. per kg. doxorubicin in 5 patients, 2) 1 mg. per kg. mitomycin C in 3 and 3) 0.6 mg. per kg. mitomycin C with 70 mg. systemic bleomycin in 3. Doxorubicin and mitomycin C were infused once preoperatively into the hypogastric arteries or the aortic bifurcation, with simultaneous hemodialysis and direct hemoperfusion to remove as much extra-regional infusate as possible and, thus, reduce the systemic toxicity of the drug. Objective responses were obtained in 4 of 7 patients with measurable tumor (57 per cent). Downstaging was obtained in 7 of 11 patients (64 per cent). All patients given doxorubicin had leukocytopenia (500 to 1,900 per mm.3) and moderate patchy alopecia, and 1 patient given mitomycin C and bleomycin had thrombocytopenia (44,000 per mm.3). However, these side effects were observed comparatively less in the patients given mitomycin C only.     

Analysis of survival after induction chemotherapy in pyriform sinus carcinoma

Three hundred seventy-one primary squamous cell carcinomas of the pyriform sinus were treated at H?pital Laennec from 1970 through 1984 and retrospectively analyzed. The local and regional treatment consisted of initial surgical resection followed by postoperative radiotherapy. Forty-three patients were not treated by induction chemotherapy; 95 patients received preoperative chemotherapy with bleomycin as a single agent; 98 patients received three preoperative courses of vincristine, methotrexate, bleomycin, or endoxan, and 46 patients were treated by three courses of induction chemotherapy consisting of cisplatin, bleomycin, methotrexate, or 5-fluorouracil. Seventy-two patients received less than 150 mg of bleomycin and 17 patients received only one or two cycles of multiple-agent chemotherapy. Survivals were higher when multiple-agent chemotherapy was employed as compared with single-agent induction chemotherapy. Further prospective investigations are necessary to confirm that induction chemotherapy enhances survival in pyriformk sinus cancers.     

Sequential combination chemotherapy consisting of vincristine, peplomycin, methotrexate, cis-diamminedichloroplatinum (II) and adriamycin in urothelial cancer

The VPM-CisA (vincristine (VCR), peplomycin (PLM), methotrexate (MTX), cisplatin (CDDP) and doxorubicin (ADM), regimen was used to treat 33 patients with urothelial tract tumors. Twenty-two patients had bi-dimensionally measurable disease parameters and 11 patients with locally advanced tumors were given postoperative adjuvant chemotherapy. The protocol consisted of 0.6 mg/m2 VCR on days 1 and 3, 3 mg/m2 PLM on days 1 to 4, 3 mg/m2 MTX on days 2 and 4, 35 mg/m2 CDDP on day 4, and 20 mg/m2 ADM on day 5. These doses were adjusted for each case: the above mentioned dose x [(80/(40+Age]2 +[(Karnofsky's performance status/100)2]. Of these patients, 28 (86 percent) were treated adequately, including 8 (36 per cent) who achieved a complete (2) or partial (6) remission. The mean duration of survival was 65.2 weeks for complete and partial responders, and 48.8 weeks for non-responders, which was not a statistically significant difference. Of 11, who were given post-operative adjuvant chemotherapy (mean observation period: 83.5 weeks) 9 were alive without evidence of disease, 1 had a recurrence 8 months after first chemotherapy, 1 died due to pulmonary and liver metastasis 2 years after the chemotherapy. Toxicity included mild myelosupression, moderate anorexia, vomiting, and severe gastric ulcer, pulmonary fibrosis.     

EORTC Genito-Urinary Group studies in advanced testicular cancer--past and future

Two hundred and twenty-eight patients with advanced testicular cancer were entered into a randomized study of chemotherapy comprising cis-platinum (P) 20 mg/m2-, days 1-5 every 3 weeks for four courses, bleomycin (B) 30 mg weekly for 12 weeks, and vinblastine (V) at either the low dose of 0.15 mg/kg or the high dose of 0.20 mg/kg on days 1 and 2 every 3 weeks for four courses. In this interim analysis, 64 patients were randomized to high dose PVB. Forty-five (71%) achieved a complete response, and 13 (25%) a partial response. Seventy patients received low dose PVB of whom 50 (71%) achieved a complete response and 16 (23%) a partial response. Thus there is no difference in the efficacy of this combination chemotherapy with respect to the dose of vinblastine, but the low dose schedule was less toxic (particularly to bone marrow). It was also apparent that the response rate varied with the volume of metastatic disease, irrespective of the dose of vinblastine. Patients with low volume metastases had a complete response rate (CR) of 88%, while those with high volume had a CR rate of 60%. In a second randomization, 68 patients achieving CR were randomized to receive either 1 year of further (maintenance) chemotherapy with cis-platinum and vinblastine, or no further chemotherapy. One of 37 patients (3%) receiving treatment and 2 of 31 patients (6%) not receiving treatment relapsed, with a follow-up of at least 10 months. Thus maintenance chemotherapy appears not to be necessary in the treatment of advanced testicular cancer.     

A case of alpha-fetoprotein producing primary intracranial embryonal carcinoma treated with combination chemotherapy with cis-platinum, vinblastine and bleomycin (author's transl)

A case of alpha-fetoprotein (AFP) producing primary intracranial embryonal carcinoma was reported with special reference to the chemotherapy. The patient was a 14-year-old male who had suffered from vomiting and disturbance of consciousness. CT scan revealed a tumor originating in the anterior part of the third ventricle and expanding into both lateral ventricles. Right frontotemporal craniotomy was performed and the tumor was totally removed under the microscope. The histological diagnosis was embryonal carcinoma. Inspite of the elevated amount of AFP in the serum, we could not verify the yolk sac element in the surgical specimen. Three months later, he became drowsy and another CT scan revealed recurrence of the tumor. Ommaya's reservoir was placed and CSF was drained to control the intracranial hypertension. But the disturbance of consciousness did not improve. We then started a combination chemotherapy with cis-platinum, vinblastine and bleomycin. Cis-platinum was given in a dosage of 20 mg/m2 body surface area as a 15 min. intravenous infusion for 5 consecutive days every 3 weeks for three courses. Vinblastine was given in a dosage of 0.4 mg/kg body weight intravenously for 2 consecutive days every 3 weeks for three courses. Bleomycin was given in a dosage of 30 mg intravenously 6 hours after vinblastine weekly for a total of 12 weeks. The AFP level of the serum and CSF was monitored every several days. After the chemotherapy, the AFP level of the serum and CSF decreased. Repeated CT scan revealed no evidence of tumor. His clinical condition improved remarkably. Toxicity was vomiting, proteinuria and leukopenia, but not so severe. Proteinuria continued after the chemotherapy, but BUN and creatinine did not elevate. It was emphasized that the combination chemotherapy with cis-platinum, vinblastine and bleomycin is effective remission-induction treatment for AFP producing primary intracranial embryonal carcinoma.     

EORTC GENITO-URINARY GROUP STUDIES IN ADVANCED TESTICULAR CANCER—PAST AND FUTURE

Two hundred and twenty-eight patients with advanced testicular cancer were entered into a randomized study of chemotherapy comprising cis-platinum (P) 20 mg/m², days 1–5 every 3 weeks for four courses, bleomycin (B) 30 mg weekly for 12 weeks, and vinblastine (V) at either the low dose of 0.15 mg/kg or the high dose of 0.20 mg/kg on days 1 and 2 every 3 weeks for four courses. In this interim analysis, 64 patients were randomized to high dose PVB. Forty-five (71%) achieved a complete response, and 13 (25%) a partial response. Seventy patients received low dose PVB of whom 50 (71%) achieved a complete response and 16 (23%) a partial response. Thus there is no difference in the efficacy of this combination chemotherapy with respect to the dose of vinblastine, but the low dose schedule was less toxic (particularly to bone marrow). It was also apparent that the response rate varied with the volume of metastatic disease, irrespective of the dose of vinblastine. Patients with low volume metastases had a complete response rate (CR) of 88%, while those with high volume had a CR rate of 60%. In a second randomization, 68 patients achieving CR were randomized to receive either 1 year of further (maintenance) chemotherapy with cis-platinum and vinblastine, or no further chemotherapy. One of 37 patients (3%) receiving treatment and 2 of 31 patients (6%) not receiving treatment relapsed, with a follow-up of at least 10 months. Thus maintenance chemotherapy appears not to be necessary in the treatment of advanced testicular cancer.     

Treatment of metastatic seminoma by chemotherapy.: an experience

PURPOSE: To describe the outcome of chemotherapy using cisplatin-based regimen, and experimental combination with carboplatin and ifosfamide to treat advanced seminoma. METHODS: From 1981 to Jan. 1999, 15 patients with Stage IIA, IIB, IIIA or IIIC metastatic seminoma and one patient with lung disease, who suffered a relapse of his primary mediastinal lesion were treated. Three of these patients had relapsed, following surveillance for Stage I testicular cancer, and another had received prophylactic radiotherapy to the retroperitoneal lymph nodes in advance. The first patient's regimen consisted of cisplatin and cyclophosphamide. Since 1983, cases have been treated with the same regimen as that used to treat non-seminomatous germ-cell tumors; cisplatin/vinblastine/bleomycin (PVB); cisplatin/vinblastine/actinomycin D/cyclophosphamide/bleomycin (VAB-6); cisplatin/etoposide/bleomycin (BEP). From 1993, six patients with non-bulky metastatic seminoma participated in a trial involving 3 courses of carboplatin (400 mg/m2) and ifosfamide (2,000 mg/m2, 3 days). RESULTS: Of the entire group, 10 patients (62.5%) achieved a CR after chemotherapy alone. Four cases who received radiation, following chemotherapy, produced CR. Surgical resection of residual tumors were performed on 2 patients. Resected tumors were fibrous and no evidence of malignancy. All those individuals who participated in this study, are alive and disease-free today, from 11 months to 18 years. Carboplatin and ifosfamide demonstrated only mild toxicity, during a 4-week cycle, with subjects being treated on an outpatient basis. CONCLUSION: As expected, the type of chemotherapy we used, to treat non-seminomatous germ-cell tumors proved to be highly effective for seminomatous types, as well. Carboplatin and ifosfamide performed well and safe, in the treatment of non-bulky metastatic seminoma. Comparative studies of long-term treatment results and QOL, using either radiotherapy or low-toxicity chemotherapy for Stage IIA disease should be undertaken.