Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors.

PURPOSE: The efficacy of paclitaxel was evaluated in combination with ifosfamide and cisplatin as second-line chemotherapy for patients with relapsed testicular germ cell tumors (GCTs). PATIENTS AND METHODS: Forty-six patients with progressive metastatic GCTs were treated with paclitaxel and ifosfamide plus cisplatin (TIP) as second-line therapy. Eligibility required that patients have both a testis primary tumor site and a prior complete response (CR) to a first-line chemotherapy program, which had been identified previously as favorable prognostic factors to conventional-dose salvage chemotherapy. RESULTS: Thirty-two (70%) of 46 patients achieved a CR to treatment. Three patients (7%) who achieved a CR relapsed after TIP chemotherapy. Twenty-nine patients are continuously disease free at a median follow-up time of 69 months, resulting in a 63% durable CR rate and a 2-year progression-free survival rate of 65% (95% CI, 51% to 79%). CONCLUSION: Four cycles of TIP as second-line therapy achieved a durable CR rate in a high proportion of patients with relapsed testicular GCT. The high CR rate emphasizes the importance of patient selection according to prognostic factors to achieve a favorable outcome to conventional-dose salvage therapy.     

Sequential dose-intensive paclitaxel, ifosfamide, carboplatin, and etoposide salvage therapy for germ cell tumor patients.

PURPOSE: To evaluate the efficacy and toxicity of sequential, dose-intensified chemotherapy with paclitaxel/ifosfamide and carboplatin/etoposide administered plus peripheral blood-derived stem-cell (PBSC) support for patients with germ cell tumors (GCT) who have unfavorable prognostic features in response to conventional-dose salvage programs. Carboplatin was dose escalated by target area under the curve (AUC; in [milligrams per milliliter] x minutes) among patient cohorts, and pharmacokinetic studies were performed for comparison. PATIENTS AND METHODS: Thirty-seven previously treated patients who had cisplatin-resistant GCT and unfavorable prognostic features for response to conventional-dose salvage therapy were treated. Two cycles of paclitaxel 200 mg/m(2) plus ifosfamide 6 g/m(2) were given 2 weeks apart with leukapheresis, followed by three cycles of carboplatin plus etoposide given 14 to 21 days apart with reinfusion of PBSCs. The dose of etoposide was 1, 200 mg/m(2), and the carboplatin target AUC ranged among cohorts from 12 to 32 (mg/mL) x min. Pharmacokinetic studies of carboplatin were performed for comparison of target to measured AUC. RESULTS: Twenty-one patients (57%) achieved a complete response and an additional two patients (5%) achieved a partial response with normal tumor markers; therefore, 23 (62%) achieved a favorable response. Eight patients relapsed, and 15 (41%) of the favorable responses remained durable at a median follow-up of 30 months. Myelosuppression was the major toxicity; 58% of carboplatin/etoposide cycles were associated with hospitalization for nadir fever. The AUC of carboplatin measured in serum was lower than the target AUC; this may be related to underestimation of the glomerular filtration rate used in the dosing formula. CONCLUSION: Dose-intense therapy with sequential, accelerated chemotherapy of paclitaxel/ifosfamide and carboplatin/etoposide administered with PBSC support was relatively well tolerated. The durable complete response proportion was substantial in patients with unfavorable prognostic features for achieving durable complete response to conventional-dose salvage programs. Optimal dosing of carboplatin in the high-dose setting warrants further investigation.     

Incidence of late-relapse germ cell tumor and outcome to salvage chemotherapy.

PURPOSE: To define the incidence, clinical features, and outcome to salvage chemotherapy in patients with late-relapse germ cell tumor (GCT) after a complete response to first-line chemotherapy. PATIENTS AND METHODS: Two patient populations were examined. First, retrospective analysis of 246 patients treated on a clinical trial with salvage chemotherapy was performed; 29 patients with late-relapse GCT were identified and evaluated for treatment outcome and survival. Salvage regimens included paclitaxel, ifosfamide, and cisplatin, single agents, or a high-dose chemotherapy program. Second, the incidence of late relapse was assessed by retrospective analysis of 551 patients after a complete response (CR) to first-line chemotherapy. RESULTS: Twenty-nine patients received salvage chemotherapy on a clinical trial for late relapse GCT. The median survival was 23.9 months. At a median follow-up of 50.6 months, there were nine survivors. The chemotherapy regimens varied, but the only CRs were observed in patients treated with paclitaxel, ifosfamide, and cisplatin. Seven (50%) of 14 patients treated with paclitaxel, ifosfamide, and cisplatin achieved a continuous CR. Among the second population of 551 patients who had previously achieved a CR to a first-line chemotherapy trial, 17 were identified as having a late relapse (3%). The median time to relapse for these 17 patients was 7.8 years. CONCLUSION: Late-relapse GCT is uncommon and is associated with a poor prognosis resulting from a high degree of resistance to chemotherapy. Chemotherapy with paclitaxel, ifosfamide, and cisplatin followed by surgery may be effective in patients with late-relapse GCT who are not considered candidates for primary surgery.     

VP-16 plus ifosfamide plus cisplatin as salvage therapy in refractory germ cell cancer

Forty-eight evaluable male patients with germ cell tumors (GCT) failing to be cured with first-line therapy were treated with VP-16 (75 mg/m2), ifosfamide (1.2 g/m2), and cisplatin (20 mg/m2) (VIP), all given daily for 5 consecutive days every 3 weeks. All patients either achieved an unresectable partial remission as their best response to induction chemotherapy (Group A), relapsed from complete remission (CR) less than or equal to 2 months after induction therapy (Group B), or had received cisplatin plus VP-16 as previous salvage therapy (Group C). Nine (19%) had extragonadal GCT, and 37 (77%) had advanced disease. Twenty-three (48%) of the patients had greater than or equal 2 prior treatment regimens. Sixteen of 48 (33%) achieved CR with VIP treatment alone or following surgical excision of residual disease. Six of 22 (27%), three of seven (43%), and seven of 19 (37%) patients from groups A, B, and C, respectively, attained a CR. The median survival time of all patients was 7 months (range 0 to 28+) with seven patients remaining continuously free of disease (four patients greater than 1 year). Myelosuppression was significant with a median WBC nadir of 900/mm2 and platelet nadir of 24,000/mm2. Fourteen (26%) had granulocytopenic fever, and renal insufficiency developed in 15%. VIP combination chemotherapy demonstrates activity in this highly unfavorable population of patients with germ cell tumors. The actual contribution of ifosfamide in this regimen is unclear, but these results compare favorably to our experience with similar patients treated with cisplatin plus VP-16 alone. Further studies with VIP as initial salvage therapy for patients with GCT are planned.     

Dexamethasone, cytarabine, ifosfamide, and cisplatin as salvage therapy in non-Hodgkin lymphoma

The authors conducted a phase II study to evaluate a new combination of chemotherapeutic drugs that includes dexamethasone, cytarabine, ifosfamide, and cisplatin as salvage therapy in non-Hodgkin lymphoma after prior exposure to both adriamycin and etoposide. All drugs were administered intravenously over 4 consecutive days. The daily dose of dexamethasone was 20 mg twice daily. The maximal daily doses of cytarabine, ifosfamide, and cisplatin were 75 mg/m2, 1,200 mg/m2, and 20 mg/m2, respectively. Cycles were repeated every 3 weeks. A total of 31 patients were entered in the trial. Thirty patients were evaluable for response. A complete response was seen in 11 patients (37%), and a partial response was noted in six patients (20%). A significantly higher complete response rate was seen in patients with relapsing non-Hodgkin lymphoma compared with those who failed to achieve a complete response with the last chemotherapy (10/14 vs. 1/16; p < 0.013). A complete response continues in two patients who received consolidation with high-dose chemotherapy for more than 49 months and more than 60 months for each patient. Median time to treatment failure and median survival were 3.3 months and 7.5 months, respectively, for the entire group and 11 months and 30 months, respectively, for complete responders. Myelosuppression was pronounced but was usually of short duration. Neutropenic fever developed in 13 patients (42%) and in 15 of 96 cycles (16%). Platelet transfusions were required in seven patients (23%). There was one drug-related death associated with myelotoxicity. Nonhematologic toxicity was not dose limiting. The authors conclude that dexamethasone, cytarabine, ifosfamide, and cisplatin is active and a relatively tolerable regime for patients with non-Hodgkin lymphoma previously treated with adriamycin and etoposide.     

Salvage chemotherapy in refractory testicular cancer

A treatment strategy for patients with refractory testicular cancer who failed in the initial therapy has not been established. Patients with metastatic testicular cancer are treated with BEP (BLM, etoposide, CDDP) therapy, which is recognized as the standard first line chemotherapy regimen. About 80% of patients attain complete remission (CR) with BEP therapy and following salvage surgery. The patients who fail to achieve CR or have recurrences during the period of follow-up will be candidates for salvage chemotherapy. Salvage chemotherapies include VIP (ETP, ifosfamide, CDDP) therapy or high dose chemotherapy with peripheral blood stem cell auto-transplantation (PBSCT); however, the effectiveness of these therapies is limited. Those who fail in these salvage therapies are treated with irinotecan hydrochloride (CPT-11) in Japan. Clinical trials with paclitaxel and gemcitabine have recently been started in the United States and Europe. Further investigations are necessary to develop more useful regimens with these novel anticancer agents for refractory testicular cancer.     

VIP化疗方案治疗小细胞肺癌的疗效观察

目的　评价VIP化疗方案 (异环磷酰胺 +顺铂 +鬼臼乙叉甙 )对小细胞肺癌 (SCLC)的治疗价值。方法　按入院顺序随机将 12 0例局限型SCLC初治患者分成VIP治疗组和EP治疗组 (顺铂 +鬼臼乙叉甙 ) ,分别治疗 3周期后评价各组的完全缓解 (CR)、部分缓解 (PR)、稳定 (SD)、进展 (PD)和总有效率 (RR) ,并比较各组的毒副反应发生率。此外 ,还对 2 5例EP方案治疗失败的SCLC患者 ,采用VIP方案解救治疗 ,观察其CR、PR、SD、PD和RR。结果　在 118例可评价的患者中 ,两方案对初治局限型SCLC患者的RR分别为89.6%和 78.3 % (P >0 .0 5 ) ,其毒性反应相当 ,但VIP方案的CR率为 43 .1% ,明显高于EP方案 ( 2 5 .0 % ) (P<0 .0 5 ) ;VIP方案对EP方案治疗无效或复发病例CR率为 13 .0 % ,PR率为 3 9.1% ,PD为 47.8% ,RR为5 2 .2 %。结论　VIP方案作为局限型SCLC患者的一线方案疗效优于标准EP方案 ,而且还可用于EP方案治疗失败病例的解救治疗。     

Salvage therapy with high-dose chemotherapy and autologous bone marrow support in the treatment of primary nonseminomatous mediastinal germ cell tumors.

The authors reported their experience with the use of high-dose chemotherapy and autologous bone marrow rescue (ABMR) as salvage therapy in the treatment of patients with recurrent and refractory primary nonseminomatous mediastinal germ cell tumors (PMGCT). Since 1987, the authors have treated 12 patients with PMGCT with high-dose carboplatin (1500 mg/m2 to 1800 mg/m2) and etoposide (1200 mg/m2 to 1350 mg/m2) (in two patients ifosfamide [10 g/m2] was added) with ABMR. Patients were either in second relapse or cisplatin refractory (progression within 4 weeks of last cisplatin dosing). They had received a median of two prior chemotherapy regimens (range, one to three), all had had prior cisplatin therapy, and most had failed ifosfamide-based therapy. Six patients were cisplatin refractory and of these only one achieved a partial response (PR) that was of short duration. It was planned that all patients would undergo two rounds of therapy; however, only 5 of 12 patients received two courses. The remainder had only one round of therapy either because of inadequate response (three patients) or excessive toxicity (four patients). There were four patients who died in the peritransplant period due to sepsis (two patients) or bleeding (two patients). The median survival of the group was 107 days (range, 14 days to 347 days). No patient achieved a complete remission, but there were six partial remissions, four with stable disease, and two with progressive disease. The use of high-dose carboplatin and etoposide with or without ifosfamide and ABMR was not effective in the treatment of this group of patients with PMGCT who were in second relapse or cisplatin refractory.     

Paclitaxel, ifosfamide, and cisplatin second-line therapy for patients with relapsed testicular germ cell cancer.

PURPOSE: To evaluate the dose, toxicity, and efficacy of paclitaxel in combination with ifosfamide and cisplatin as salvage therapy for patients with relapsed testicular germ cell tumors (GCTs). PATIENTS AND METHODS: Thirty patients with previously treated GCTs were treated with paclitaxel and ifosfamide plus cisplatin (TIP) as second-line therapy. All had favorable prognostic features for response (testis primary tumor site and prior complete response to first-line chemotherapy program). Four cycles of paclitaxel, ifosfamide 5 g/m(2), and cisplatin 100 mg/m(2) were given 21 days apart with granulocyte colony-stimulating factor support, followed by resection of radiographic residua. The dose of paclitaxel was increased among cohorts with dose levels of 175, 215, and 250 mg/m(2); the largest dose was selected for the phase II part of the trial. RESULTS: Twenty-three (77%) of 30 patients achieved a complete response to chemotherapy alone, and one patient achieved a durable partial response with normal tumor markers. Therefore, 24 (80%) achieved a favorable response. Eleven patients with normalized markers after chemotherapy underwent resection of residual tissue, with only necrosis found in 10 and mature teratoma in one. Two patients relapsed, and 22 (73%) of the favorable responses remain durable at a median follow-up duration of 33 months. Myelosuppression was the major toxicity, and two patients had grade 3 neurotoxicity. CONCLUSION: Four cycles of TIP was associated with a high proportion of patients who achieved a complete response, a lack of relapse, and relative tolerability as an ifosfamide-containing salvage regimen for testicular GCTs. The high durable complete response proportion emphasizes the importance of patient selection according to prognostic factors for a favorable outcome to conventional-dose salvage therapy.     

Ifosfamide in germ cell tumors

Ifosfamide has always had significant single-agent activity in patients with germ cell tumors. We first began studies of cisplatin + ifosfamide combination chemotherapy as salvage chemotherapy in 1982. The regimen of etoposide (VP-16) + ifosfamide + cisplatin (VIP) was initially utilized as third-line chemotherapy. Even in this refractory setting, we were able to cure a small cohort of patients. Ifosfamide-cisplatin combination chemotherapy then became a standard second-line chemotherapy program, and achieved a 25% cure rate. Subsequent phase III studies compared VIP to bleomycin + etoposide + cisplatin (BEP) as initial chemotherapy. Although the results of the ifosfamide-based regimen were slightly better, there was no statistically significant difference and BEP was less toxic. However, for individual patients with concern for bleomycin-induced pulmonary fibrosis, VIP remains an attractive first-line regimen.     

Etoposide, ifosfamide, and cisplatin in extensive small cell lung cancer.

From December 1987 through April 1989, 40 patients with extensive-stage small cell carcinoma of the lung were enrolled in a Hoosier Oncology Group (HOG) trial using etoposide, ifosfamide, and cisplatin (VIP). Patients with extensive disease were eligible if they had not received prior chemotherapy, had a Karnofsky performance status of 50 or more, and had adequate renal function (creatinine, less than 1.5 mg/dl) and bone marrow reserve (granulocyte count, greater than or equal to 2500/microliters; platelets, greater than or equal to 125,000/microliters). Doses of therapy were: etoposide 75 mg/m2/day on days 1 to 5, ifosfamide 1.2 g/m2/day on days 1 to 5, and cisplatin 20 mg/m2/day on days 1 to 5. The first 11 patients received a 5-day course; this was repeated every 21 days for four cycles, but therapy was shortened to 4 days when unacceptable toxicity was noticed in these patients. Overall, 14 (37%) had a complete remission (overall response rate, 71.1%) with a median survival of 42 weeks (28 weeks on 5-day regimen and 45 weeks on 4-day regimen). There were five early deaths. Although toxic, VIP produces a high complete remission rate in patients with extensive disease and warrants further evaluation. A prospective randomized trial comparing cisplatin and etoposide to the VIP regimen is underway through HOG.     

Salvage chemotherapy for patients with germ cell tumors. The Memorial Sloan-Kettering Cancer Center experience (1979-1989).

Twenty-eight of 124 (23%) advanced germ cell tumor (GCT) patients who were treated on four successive platin-based induction regimens and who failed to achieve a durable complete response (CR) remain alive (median follow-up, 50 months). An analysis of prognostic factors for response and survival was conducted on the 94 patients who received salvage chemotherapy. Survival and/or response to salvage therapy were significantly enhanced for patients with a prior CR to induction chemotherapy, treatment with a cisplatin-based salvage regimen, a testis primary site, a normal serum human chorionic gonadotropin level, a normal serum lactate dehydrogenase level, one site of metastasis, and an Indiana Class of 6 or less. Patients with a prior incomplete response (IR) had a particularly poor prognosis (P = 0.00007) with only 4 of 52 (9%) patients alive (median follow-up, 37 months) compared with 15 of 42 (36%) patients with a prior best response of a CR (median follow-up, 35 months). The poor survival of patients who fail to achieve a durable CR to induction chemotherapy warrants the continued investigation of new salvage therapy. The identification of prognostic features may direct salvage therapy and aid in the interpretation of clinical trials of salvage regimens.     

Should high-dose chemotherapy be used to consolidate second or third line treatment in relapsing germ cell tumours?

Thirty consecutive patients with relapsing germ cell tumours (GCT) were treated with induction chemotherapy and high-dose chemotherapy consolidation (HDCT). Overall, 47% were progressionfree and 53% were alive with a median follow up of 40 months. Initially, HDCT was given as consolidation of third line VIP (etoposide/ifosfamide and cisplatin), following failure of a weekly cisplatin regimen. During 1995, paclitaxel was introduced into second line therapy with cisplatin and ifosfamide (TIP), with immediate consolidation using HDCT. At the same time the carboplatin dosing calculation was changed and an area under the curve (AUC) formula rather than by mg/m² was used to calculate this. The main determinant of post-treatment renal dysfunction was pretreatment renal function rather than the AUC dose of carboplatin. Only a raised LDH prior to induction or absolute refractory disease in response to induction chemotherapy predicted poor survival following HDCT. In patients relapsing following HDCT, the outcome was poor with many patients relapsing in the central nervous system and other new sites of disease. Further responses were seen to chemotherapy or radiotherapy but these were not sustained. The failure to improve results when HDCT was used as second line rather than third line chemotherapy consolidation was disappointing and adds to further uncertainty of the role of this approach as far as timing and the ideal preparative regimen are concerned.     

Two-drug therapy in patients with metastatic germ cell tumors.

Eighty-two patients with metastatic germ cell tumors (GCT) treated with two-drug therapy consisting of etoposide and cisplatin were evaluated for late relapse. Good-risk GCT was defined using Memorial Sloan-Kettering Cancer Center (MSKCC) criteria. Etoposide was given at 100 mg/m2 on days 1 to 5 and cisplatin was given at 20 mg/m2 on days 1 to 5; therapy was recycled at 21 days with delays up to 7 days for a leukocyte count of less than 3000/microliters or a platelet count of less than 100,000/microliters. Drug doses were not attenuated for myelosuppression. Seventy-six of 82 evaluable patients achieved a complete response (CR). Seventy-two patients had a CR to chemotherapy alone. Forty-six (56%) patients had excision of residual abnormalities: 11 had teratoma in the resected specimen, 31 had necrotic debris or fibrosis, and 4 had a CR after chemotherapy plus complete excision of residual viable GCT. Six patients had an incomplete response to chemotherapy; one of these patients had unresectable mature teratoma and remains progression-free. The median etoposide dose (+/- standard deviation [SD]) was 500 mg/m2/course (+/- 35 mg/m2) and the median cisplatin dose (+/- SD) was 100 mg/m2/course (+/- 6 mg/m2). Nine patients experienced a relapse at 6 to 17.5 months; two patients with nonseminomatous GCT were salvaged by chemotherapy and one patient with seminoma was salvaged by chemotherapy and radiation therapy. The three patients who were salvaged by additional therapy are disease-free at 59 to 63 months. Seventy-one patients (87%) remain disease-free with a median follow-up time of 63 months (range, 33 to 92 months). No relapses have occurred beyond 17.5 months. Etoposide and cisplatin therapy at these doses and schedule results in durable CR without late relapse.     

Actinomycin D revisited in testicular cancer. A case report

BACKGROUND: Between 20-30% of patients with advanced germ cell tumors relapse or fail to achieve a complete response to conventional cisplatin based chemotherapy. Ifosphamide has been used very effectively in combination with cisplatin and etoposide (VIP) or in combination with cisplatin and vinblastine (VeIP). Actinomycin D with chlorambucil and methotrexate was widely used in the 1960s with complete responses in 20% of patients and long term survival of 6-10%. There exists no information on the use of actinomycin as a salvage in cisplatin refractory patients. METHODS AND RESULTS: One patient with metastatic germ cell tumor who failed chemotherapy with cisplatin and ifosphamide was successfully treated with an actinomycin D based regimen. CONCLUSIONS: Actinomycin D is an active agent in testicular cancer and maybe used in patients refractory to platinum.     

High-dose chemotherapy and autologous bone marrow rescue for patients with refractory germ cell tumors. Early intervention is better tolerated.

Therapy with high-dose carboplatin plus etoposide-based chemotherapy plus autologous bone marrow rescue (AUBMR) was administered to 29 patients with advanced germ cell tumors (GCT) refractory to cisplatin-based chemotherapy. Two groups of patients with refractory disease were treated. Sixteen patients had been identified as "poor risk" at diagnosis and had an inappropriately slow decline of serum tumor markers after two cycles of induction cisplatin-based therapy (Group A). In addition, 13 patients were treated who had never had a complete response (CR) or had relapses after ifosfamide-based salvage chemotherapy (Group B). Patients in Group A were treated with high-dose carboplatin etoposide, and patients in Group B received high-dose carboplatin, etoposide, and cyclophosphamide. Fifteen of 29 (52%) patients had a CR (9, Group A; 6, Group B). The patients in Group A had fewer hematologic toxic effects, and the median number of days from day 0 to a granulocyte count greater than 0.5/microliters was 16 and to a platelet count of more than 50/microliters was 15, compared with 22 days and 23 days in Group B, respectively. There were fewer episodes of culture-positive sepsis in Group A (12%) compared with Group B (26%), and the only treatment-related death occurred in Group B. Therapy with high-dose carboplatin plus etoposide-based chemotherapy plus AUBMR is effective for patients with GCT refractory to regimens of cisplatin with or without ifosfamide. Early use of high-dose chemotherapy reduces hematologic toxic effects and allows patients to start treatment in a more predictable fashion after cytoreduction, rather than when the disease is progressing rapidly.     

Salvage chemotherapy for patients with advanced pure seminoma.

PURPOSE: We describe the response to conventional or high-dose salvage chemotherapy in patients with advanced seminoma who experience disease progression after receiving first-line platinum-based treatment. PATIENTS AND METHODS: Twenty-seven patients with progressive, advanced, pure seminoma were treated with salvage chemotherapy. Fifteen patients were treated with conventional-dose cisplatin-and-ifosfamide combination chemotherapy. Twelve patients were treated with high-dose chemotherapy followed by autologous stem-cell rescue. RESULTS: Fifteen patients (56%) achieved a complete response (CR), nine achieved CR with a conventional-dose cisplatin and ifosfamide program, and six experienced CR after high-dose chemotherapy. Fourteen patients (52%) are alive and disease-free, with 13 (48%) continuously disease-free at a median follow-up of 72 months. Twelve (57%) of 21 patients whose pretreatment tumors were studied morphologically were found to have seminoma with atypia. Eight patients underwent resection after salvage chemotherapy; six with histologic findings of necrotic debris/fibrosis alone are alive and disease-free at last follow-up. Both patients with viable seminoma found at surgery died of disease. CONCLUSION: Most patients with advanced seminoma are cured with standard first-line programs of cisplatin and etoposide with or without bleomycin. A small minority of patients with pure seminoma have resistant tumors and require salvage chemotherapy. In this setting, approximately 50% of patients with recurrent pure seminoma achieve durable CR with conventional or high-dose salvage chemotherapy. Identification of biologic markers to predict clinical outcome and an enhanced understanding of the basic biologic features of seminoma may lead to improvements in the management of this disease.     

BOP/VIP--a new platinum-intensive chemotherapy regimen for poor prognosis germ cell tumours.

Ninety-one patients with poor prognosis non-seminomatous germ cell tumours (NSGCT) were treated with an initial intensive chemotherapy schedule. Suitable patients fulfilled one or more of the following criteria: lymph node metastases greater than 10 cm diameter; liver, brain or bone metastases; serum HCG level greater than 50,000 IU/L; and extragonadal primary tumours. Treatment consisted of 3 cycles of bleomycin, vincristine and cisplatin (BOP) administered at 10 day intervals, followed by 3 cycles of etoposide, ifosfamide and cisplatin (VIP) at 21 day intervals. A total of 64 patients (70%) achieved a complete remission. This comprised 46 patients who received BOP/VIP only, and 18 patients who received additional chemotherapy after BOP/VIP. Of these 64 patients, 51 underwent complete surgical resection of residual masses, including 11 in whom there was evidence of teratoma with cellular atypia or non-germ cell cancer in the resected tissue. A further 9 patients had persisting unresected radiological masses in the presence of marker complete remission. The overall response rate was 80%. Currently 57 patients (63%) remain alive and free from disease progression. The median follow-up period is 90 weeks (range 24-206 weeks), with a 2 yr actuarial progression-free survival of 66% (95% c.i. 55-77%). Major toxicity was myelosuppression, occurring during the VIP arm of therapy, with a median nadir WBC of 1.1 x 10(9)/L and median platelet count of 51 x 10(9)/L. Other toxicity included peripheral neuropathy (WHO Grade 2 and 3 in 22%). We conclude that treatment results with the BOP/VIP schedule in this poor prognosis patient group are at least comparable with other schedules, and toxicity is manageable.(ABSTRACT TRUNCATED AT 250 WORDS)     

Autogreffe dans les cancers du testicule

The majority of patients with advanced germ cell tumours (GCT) achieve a continuous and complete response to first-line cisplatin combination chemotherapy. Nevertheless, patients with poor prognosis respond less well. Moreover, patients with progressive or recurrent GCT require effective salvage therapy. Using conventional-dose chemotherapies in salvage therapy, 20 to 30% of patients will become long-term survivors. Studies of high-dose chemotherapy have reported promising results on its effectiveness in treating recurrent GCT. However, randomized trials do not demonstrate an impact on the clinical benefit of high-dose chemotherapy as a first-line treatment for patients with poor prognosis or recurrent GCT. A better understanding of prognostic factors, the use of new drugs in high-dose protocols and the evaluation of targeted molecular therapies could increase the clinical benefit of high-dose strategies.     

Effective salvage chemotherapy with etoposide, dactinomycin, and methotrexate in refractory germ cell cancer. Australasian Germ Cell Trial Group

Fifty-one patients with advanced germ cell malignancy who had either failed to achieve complete remission with initial cisplatin, vinblastine, and bleomycin chemotherapy or who had relapsed after complete response (CR) to this therapy and then proven refractory on retreatment, were treated with etoposide (75 mg/m2 for 3 days), dactinomycin (1 mg/m2 day 1), and methotrexate (30 mg/m2 day 1) (EAM) every 3 weeks. Courses were continued until maximum response without empirical limit, and if complete remission was achieved, two courses of consolidation therapy were given before cessation of treatment. Thirteen patients (25%) were complete responders with residual masses containing fibrosis or benign teratoma being subsequently resected in seven patients. Two patients had persisting viable carcinoma within residual masses that were completely resected, leaving no evidence of disease (NED); the combined CR plus NED rate was 29%. The only pretreatment factor significantly influencing this response rate was tumor volume. Toxicities were moderate, with leukopenia being observed in 28% of patients, but it was severe in only 2%. There was one death from septicemia. Severe nausea and vomiting occurred in only 9% of patients and treatment-related stomatitis was observed in 42%. All patients achieving CR plus NED have been followed for a minimum of 5 years and no relapses have occurred, suggesting that these patients are cured. Unlike other regimens of salvage chemotherapy, this treatment program did not contain cisplatin and it is contended that a completely noncrossresistant drug regimen based on etoposide provides the opportunity to further improve the curability of patients with advanced germ cell cancer.