Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.     

Clinical study for management of supportive treatment for high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) for intractable testicular tumor

The side effects of high-dose anti-cancer drug chemotherapy with peripheral blood stem cell transplantation (PBCST) for the treatment of intractable testicular tumor are very serious. In particular, agranulocytosis in bone marrow suppression may be life threatening. In this study, we examined opportunistic infectious diseases and preventive counter measures in the compromised conditions of anti-cancer drug chemotherapy. The patients underwent anti-cancer drug chemotherapy with PBCST for the treatment of intractable testicular tumors at Kobe University Hospital from September 1996 to September 2002. The high-dose chemotherapy regimen consisted of total doses per course of 1,250 mg/m2 carboplatin, 1,500 mg/m2 etoposide, and 7,500 mg/m2 ifosfamide. Twenty-four men (median age, 30 years; range, 18-70 years) received 50 courses of chemotherapy in total. The nadir of peripheral leukocyte counts was less than 1,000/mm3 in all courses, and the mean period was for 7.1 days. None of these patients developed critical sepsis leading to disseminated intravascular coagulation or treatment-related death. Our detailed data show that we can perform high-dose anti-cancer drug chemotherapy with PBSCT for intractable testicular tumors without serious infectious complications if we take sufficient preventive countermeasures for infectious diseases.     

Two-step ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer: a case report]

A 35-year-old male had advanced nonseminomatous germ cell tumor (stage IIIC, embryonal cell carcinoma) which proved refractory to conventional PVB combined chemotherapy. He was then treated with an ultra high-dose chemotherapy consisting of carboplatin (1.5 g/m2) and etoposide (1.3 g/m2), followed by the transplantation of peripheral blood stem cells (PBSCT) with a total of 1.9 x 10(5)/kg granulocyte colony-forming cells (CFU-GM). Because he developed lung metastasis, escalated doses of carboplatin (2.0 g/m2), and etoposide (1.8 g/m2) combined with cyclophosphamide (7.0 g/m2) were given with peripheral blood stem cell transplant of 3.2 x 10(5)/kg CFU-GM. He has remained free of any recurrence without maintenance therapy.     

Clinical study of high-dose chemotherapy with peripheral blood stem cell transplantation for poor-risk germ cell tumor

Between January 1997 and December 1998, six patients with germ cell tumor were treated with high-dose CEC: carboplatin (1,500 mg/m2), etoposide (1,200 mg/m2) and cyclophosphamide (100 mg/kg), followed by peripheral blood stem cell transplantation (PBSCT) at Nagoya University Hospital. Four patients received one cycle of high-dose CEC and two received two cycles. The reasons why the high-dose CEC was administered included: 1) refractory to the induction chemotherapy (AFP/beta-HCG elevated during the induction chemotherapy or prolonged half-life of each marker) in three patients, 2) relapse in two patients, and 3) consolidation in one with unresectable mediastinal residual tumor. There were no treatment-related deaths and grade 1 hepatotoxicity occurred in one (17%) patient. The median duration (range) from PBSCT until a granulocyte count of 500/microL and a platelet count of 50,000/microL was 8.5 (8-11) and 11 (9-16) days, respectively. Of the six patients studied, 5 responded to the treatment; two achieved a complete response (CR) and three achieved a partial response (PR). One patient achieving a CR and two achieving a PR remained in complete remission after 23 to 24 months of follow-up, while the remaining patients with a CR, a PR and an incomplete response died of the disease. High-dose CEC could be administered without serious toxicity but the effectiveness of high-dose CEC for the poor-risk patients with germ cell tumor needs to be further investigated.     

High-dose chemotherapy with peripheral blood stem cell autotransplantation for patients with poor-risk testicular germ cell tumors--pilot study of the Japan Blood Cell Transplantation Study Group

The efficacy and toxicity of a single cycle of high-dose chemotherapy with peripheral blood stem cell autotransplantation (PBSCT) in patients with poor-risk testicular germ cell tumors (GCT) enrolled in the Japan Blood Cell Transplantation Study Group was investigated. Previously untreated poor-risk testicular GCT patients were treated with BEP therapy (cisplatin, etoposide and bleomycin) with or without high-dose chemotherapy (carboplatin, etoposide and ifosphamide) followed by PBSCT. Patients were qualified for a change to high-dose chemotherapy if elevated serum tumor markers (human chorionic gonadotropin-beta, alpha-fetoprotein and lactate dehydrogenase) was observed after 3 cycles of BEP therapy. Eighteen patients were treated with BEP therapy alone and 16 with BEP and high-dose chemotherapy. At the completion of high-dose chemotherapy, all tumor markers had returned to normal in 6 patients. Among them, 1 had only teratoma found at resection and 5 had carcinoma resected. Nine patients who had persistent elevation of any tumor marker were treated with high-dose chemotherapy or another anticancer drug. Thirteen are alive (81%) and 9 (56%) are continuously disease-free at a median follow up of 11 months. The median time from PBSCT to a granulocyte count > 500/microL was 9.5 days and to a platelet count > 50,000/microL was 13 days.     

High-dose chemotherapy followed by peripheral blood stem cell transplantation in advanced extragonadal germ cell tumor--a case report]

We reported the experience of high-dose chemotherapy (HDC) combined with peripheral stem cell transplantation (PBSCT) in 29 years-old man with advanced retroperitoneal germ cell tumor accompanied with left supraclavicular lymph node metastases, who obtained complete remission after comprehensive treatment. The initial levels of serum AFP, hCG and beta-hCG were high at 30.2 ng/ml, 14,000 mIU/ml and 66 ng/ml, respectively. After 3 courses of chemotherapy (BEP regimen), while left supraclavicular lymph node swelling was disappeared, the retroperitoneal mass lesion persisted on CT scan. Not all of 3 markers fell to the normal range. After myelosuppressive chemotherapy (etoposide 500 mg/m2 Day 1-3), PBSCs were collected by two consecutive apheresises on Day 17 and 18. In total, 19.5 x 10(6)/kg CD 34 positive cells were obtained. The patient underwent PBSCT (all CD 34 positive cells were infused) on Day 0 following HDC (CBDCA 250 mg/m2/day, etoposide 300 mg/m2/day, IFM 1.5 g/m2/day, Day-7(-)-3, respectively). He became severely leukopenic and thrombopenic with nadir of 200/microliter on Day 6 and 2 x 10(4)/microliter on Day 2, respectively. By administration of platelet transfusion and G-CSF, the white blood cell counts and thrombocyte counts recovered to 6,400/microliter and 4.1 x 10(4)/microliter on Day 10, respectively. Microbiologically enterocolic and respiratory tract infections occurred with elevated body temperature (> 40 degrees C). Antibiotic and antimycotic treatments were continued until disappearance of all clinical and microbiological evidence. He was kept for 10 days in clean room. After HDC, all markers fell to the normal range, but the retroperitoneal residual mass still persisted. Resection of the residual mass and retroperitoneal lymph node dissection were performed with pathological examination revealing tissue necrosis without viable cell. The patient has survived with no sign of the disease for 9 months.     

Refractory germ cell cancer of testis treated by salvage high-dose chemotherapy: report of three cases

We reported three cases (42, 20 and 18-year-old men) of advanced nonseminomatous testicular germ cell cancer treated by salvage high-dose chemotherapy (HDC) supported by peripheral blood stem cell autotransplantation. Two cases which had been refractory to (B) EP (bleomycin, etoposide, cisplatin) and VIP (etoposide, ifosfmide, cisplatin) chemotherapies received one course of high-dose CEI (carboplatin 1,250 mg/m2, etoposide 1,500 mg/m2 and ifosfamide 7.5 g/m2), and the other case had been refractory to PVB (cisplatin, vinblastine, bleomycin) and VIP chemotherapies received one course of high-dose CEI and high-dose CCT (carboplatin 800 mg/m2, cyclophosphamide 6 g/m2 and thiotepa 720 mg/m2). Only one case achieved an incomplete remission by HDC, which was verified as a pathological complete response at the following salvage surgery, and has been alive with no evidence of disease for 68 months. The others achieved no change of disease following HDC and died from cancer progression. Hepatotoxicity, neurotoxicity and severe depression occurred, but not fatal in 2 cases.     

A case of therapy-related leukemia/myelodysplastic syndrome following treatment of refractory testicular germ cell tumor

We report a patient with a refractory testicular non-seminomatous germ cell tumor (NSGCT) who developed therapy-related leukemia (TRL) after undergoing salvage chemotherapy and multiple operations for repeat recurrences. Fifty months after the initial therapy, pancytopenia and myeloblasts were observed in the patient's peripheral blood while the patient was undergoing salvage chemotherapy for a fifth recurrence. A bone marrow examination showed evidence of myelodysplastic syndrome (MDS) and refractory anemia with excess of blasts in transformation (RAEB in T) under French-America-British (FAB) classification. Cytogenetic 5q-/7q- abnormalities were also observed. The patient had received a total dose of 189g/m2 of Ifosfamide, 8,250mg/m2 of Etoposide and 1,450 mg/m2 of Cisplatin; therefore, he was diagnosed as having TRL/MDS. The patient has received induction chemotherapy for TRL with Cytarabine, Daunorubicin and Fludarabine while a bone marrow transplantation has been scheduled. Recently, TRL associated with chemotherapy are being reported with increasing frequency in the literature. Since early detection and treatment are necessary for the management of TRL, peripheral blood examinations should be performed after a diagnosis of refractory germ cell tumor has been made. If pancytopenia is detected, bone marrow and cytogenetic examinations should be immediately performed to rule out TRL.     

High-dose chemotherapy with peripheral blood stem cell transplantation for advanced testicular cancer

Between June 1998 and August 2000, five patients with germ cell tumor were treated with high-dose CEI: carboplatin (1,250 mg/m2), etoposide (1,500 mg/m2), and ifosfamide (7.5 g/m2), followed by peripheral blood stem cell transplantation (PBSCT) at Yokohama City University Hospital. All patients were classified into either poor risk group of International Germ Cell Consensus Classification or advanced extent of Indiana University stage, and received one cycle of high-dose CEI after 4-6 cycles of standard PEB (cisplatin, bleomycin, vinblastin) therapy. Three of the patients achieved complete response, one achieved partial response and one achieved no change after whole treatment. There were no fatal complications and no treatment-related deaths.     

Failure of high-dose cyclophosphamide and etoposide combined with double-dose cisplatin and bone marrow support in patients with high-volume metastatic nonseminomatous germ-cell tumours: mature results of a randomised trial

OBJECTIVES: To assess the impact on survival of high-dose chemotherapy with haematopoietic support in patients with high-volume, metastatic nonseminomatous germ cell tumours. METHODS: One hundred fifteen patients were randomised to receive either four cycles every 21 d of vinblastine (0.2 mg/kg on day 1), etoposide (100 mg/m2/d on days 1 through 5), cisplatin (40 mg/m2/d on days 1 through 5), and bleomycin (30 mg on days 1, 8, and 15) (arm A), or a slightly modified regimen followed by a high-dose chemotherapy including etoposide (350 mg/m2/d on days 1 through 5), cisplatin (40 mg/m2/d on days 1 through 5), and cyclophosphamide (1600 mg/m2/d on days 2 through 5) (arm B). RESULTS: In an intent-to-treat analysis, there were 32 (56%) and 24 (42%) complete responses in arms A and B, respectively (p=0.099). After a median follow-up of 9.7 yr, 31 and 27 patients have continuously shown no evidence of disease in arms A and B, respectively. There was no significant difference between the overall survival curves (p=0.167). According to the International Germ Cell Cancer Collaborative Group prognostic classification, the 5-yr survival rates were 88% and 82% in the intermediate group and 69% and 44% in the poor group (p=0.045) in arms A and B, respectively. CONCLUSIONS: This trial failed to demonstrate an impact on response and survival of high-dose chemotherapy with haematopoietic support in first-line treatment of patients with high-volume, metastatic nonseminomatous germ cell tumours.     

High-dose chemotherapy with autologous bone marrow transplantation as treatment for relapsing testicular cancer

In testicular cancer the tumor shows a high response rate to chemotherapy with dose responsiveness. However, when it is treated with high-dose chemotherapy, myelosuppression is severe. To overcome this problem, autologous bone marrow transplantation has been attempted. This is a report of an 18-year-old man with advanced nonseminomatous testicular cancer (stage IIB, embryonal carcinoma and teratoma) with relapse after first course of therapy. He was treated with high-dose chemotherapy (etoposide 1,750 mg/m2, cisplatin 200 mg/m2, cyclophosphamide 60 mg/kg) and with autologous bone marrow transplantation. This patient has been in complete remission for more than 15 months without severe side effects or complications. We consider this a striking response to treatment in an early phase of relapsing testicular cancer.     

Clinical results of super high-dose chemotherapy with peripheral blood stem cell transplantation for patients with advanced germ cell tumor

We examined the clinical results of super high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) in 14 patients with poor-risk advanced germ cell tumors. The mean number of nadir white blood cells was 205 +/- 126/microliter; the mean period of number of white blood cells fewer than 1,000/microliter was at 8-10 days (mean +/- SD; 9.2 +/- 0.92). The nadir number of blood platelet cells was 1.7 +/- 0.70 x 10(4)/microliter; the mean period of number of platelet cells fewer than 5 x 10(4)/microliter was at 12.6 +/- 2.17 days. Of 10 patients treated with super high-dose chemotherapy with PBSCT as induction therapy, 8 patients (80%) showed that the serum tumor marker returned within the normal range after super high-dose chemotherapy. Of 8 patients, 7 underwent resection of the residual tumor. Surgical or pathological CR was obtained in 5 of these 7 patients, 4 patients of whom were alive with no evidence of disease 29 to 49 months after initial consultation: the other patient died with recurrence 20 months after initial visit. On the other hand, super high-dose chemotherapy with PBSCT was performed for one patient as consolidation, and for 3 patients with recurrence. Of these 4 patients, one died from disease 6 months after detection of recurrence. The other 3 patients were alive with no evidence of disease at 7-37 months after initial visit. The 1- and 3-year disease-free survival rates were 88% and 72%, respectively. In conclusion, super high-dose chemotherapy with PBSCT can be done safely and could be useful for patients with poor-risk germ cell tumor.     

Testicular function in patients with testicular cancer treated with bleomycin-etoposide-carboplatin (BEC(90)) combination chemotherapy

OBJECTIVE: To investigate the impact of bleomycin-etoposide-carboplatin combination chemotherapy on long-term fertility in patients with testicular germ cell tumors.METHODS: Twenty-five patients with high risk stage I and IM non-seminomatous germ cell tumors (NSGCT, Group A) and 44 with advanced seminoma or NSGCT (Group B) were treated with bleomycin 30 mg (days 2, 9, 16), etoposide 165 mg/m(2) (days 1-3) and carboplatin 400mg/m(2) or AUC 5 (day 1) (BEC(90)). Treatment was repeated every 3 weeks. Group A patients received 2 cycles of BEC(90), while Group B ones received 4 to 5 cycles of BEC(90). Sperm count and hormonal analyses were examined pre- and post-chemotherapy. Counts were classified as normospermia (NS) if >20 x 10(6)ml(-1), oligospermia (OS) if 1-20 x 10(6)ml(-1) and azoospermia (AS) if <1 x 10(6)ml(-1). RESULTS: Patients were followed for a median of 2.9 years post-chemotherapy. The post-orchidectomy median luteinizing hormone (LH) serum levels were slightly above the upper normal limit while the serum levels of follicle stimulating hormone (FSH) and testosterone (T) were within the reference interval. Thirty-eight (55%) patients had NS pre-chemotherapy. None of the 14 NS patients who received 2 cycles of BEC(90) had AS post-chemotherapy, while only 1 of the 24 NS patients who were treated with > or =4 cycles of BEC(90) had AS post-treatment. Among the NS patients, 93% and 83%, respectively, remained NS following chemotherapy. Overall, 90% of patients had recovery (61% NS, 29% OS) of spermatogenesis after treatment. The median FSH serum values were significantly elevated at least 1-year post-chemotherapy when compared with the pre-treatment levels. Eighteen months post-chemotherapy the median FSH values had returned to the reference limits. Serum LH and T levels were unaffected by treatment. The pre-treatment sperm count and the bulk of disease were significantly associated with recovery of spermatogenesis. No association was found between recovery of spermatogenesis and 2 or > or =4 cycles of chemotherapy, age > or =30 years and post-chemotherapy lymph node dissection. Thirteen patients (4 with OS) fathered 16 children. No congenital abnormalities occurred in any of these children. CONCLUSION: The BEC(90) regimen has no major effect on fertility and Leydig cell function. However, carboplatin-based chemotherapy has been proved less effective than cisplatin-based chemotherapy and is not currently used in the treatment of testicular cancer.     

Gastrointestinal hemorrhage as first manifestation of metastatic testicular tumor

We report a case of a man with a testicular mixed germ cell tumor in whom the first symptom was severe anemia secondary to upper gastrointestinal bleeding from a metastatic pure choriocarcinoma. He underwent ileal enterectomy, radical orchiectomy, and several cycles of chemotherapy (cisplatin, etoposide, and bleomycin). He died within 41 days of diagnosis.     

High dose chemotherapy including paclitaxel (T-ICE) combined with peripheral blood stem cell transplantation for male germ cell tumor. Preliminary report

AIM: To evaluate the feasibility and usefulness of high dose chemotherapy including paclitaxel (T-ICE) combined with peripheral blood stem cell transplantation (PBSCT) for male germ cell tumor. METHODS: Five male patients with advanced germ cell tumor underwent 1-6 courses of high dose chemotherapy including paclitaxel (T-ICE; 175 mg/m2 of paclitaxel, 1250 mg/m2 of carboplatin, 1500 mg/m2 of etoposide and 7.5 g/m2 of ifosfamide) with PBSCT after 2-3 courses of induction chemotherapy (PEB or VIP). RESULTS: In all patients, serum marker levels decreased to within the normal range by T-ICE. Two patients underwent resection of residual tumor. In one patient, viable cancer cells were detected in resected lymph node tissue and adjuvant chemotherapy was then performed. Although the follow-up period was short (7-15.5 months), four of the five patients (80%) showed no evidence of recurrent disease. No significant differences in side-effects were noted between T-ICE and conventional high dose ICE, which was previously performed in 39 patients at the Division of Urology, Kobe University Graduate School of Medicine, Japan. CONCLUSIONS: High dose chemotherapy, including T-ICE, combined with PBSCT showed an almost identical degree of side-effects as seen in previous high dose chemotherapy without paclitaxel. Although 80% of the patients showed no evidence of disease so far, the efficacy of T-ICE should be evaluated with more patients and longer follow up.     

Nerve-sparing retroperitoneal lymph node dissection for advanced testicular cancer after chemotherapy

BACKGROUND: Nerve-sparing techniques are commonly used in retroperitoneal lymph node dissection (RPLND) in patients with early stage testicular germ cell tumors to preserve postoperative ejaculation. The indications for nerve-sparing procedures have been extended to patients who have residual retroperitoneal tumor postchemotherapy with an increase in the incidence of local recurrence. Here, we report on 26 Japanese men with advanced testicular cancer who underwent nerve-sparing RPLND after partially successful chemotherapy. METHODS: Between January 1995 and December 2000, 26 patients with metastatic or recurrent testicular cancer underwent nerve-sparing RPLND after chemotherapy. Eight patients had seminoma and 18 had non-seminoma. Three patients received high-dose chemotherapy with carboplatin (250 mg/m2 per day x 5 days), etoposide (300 mg/m2 per day x 5 days) and ifosfamide (1.5 g/m2 per day x 5 days) in combination with peripheral blood stem cell transplantation. RESULTS: In all cases, lumbar splanchnic nerves were preserved macroscopically during the operation, at least unilaterally. Twenty-two patients (84.6%) achieved antegrade ejaculation during a mean follow-up at 3.9 months (range: 1-7 months). Three patients have fathered children. Only one patient suffered a retroperitoneal recurrence during a median follow-up at 25.8 months (range: 6-76 months). CONCLUSION: Nerve-sparing procedures for RPLND are appropriate for patients with metastatic testicular cancer, even after chemotherapy. The procedure preserves ejaculatory function in the majority of the patients without increasing the risk of local recurrence. Nerve-sparing RPLND improves the quality of life in patients who require postchemotherapy RPLND to treat residual tumor.     

Health-related quality of life after chemotherapy for advanced germ cell tumors: A comparison of standard-dose and high-dose chemotherapy

BACKGROUND: The objective of this study was to evaluate the health-related quality of life (HRQoL) in patients with germ cell tumors who received standard-dose chemotherapy or high-dose chemotherapy combined with peripheral blood stem cell transplantation (PBSCT), and to compare the HRQoL of these patients with patients who had undergone surveillance therapy only. METHODS: Among the 102 patients included in this study, 38 underwent standard-dose cisplatin-based combination chemotherapy alone, 24 received high-dose chemotherapy with PBSCT following standard-dose chemotherapy, and 40 underwent surveillance monitoring. HRQoL was evaluated using the SF-36 survey, which contains 36 questions that assess eight quality-of-life aspects, including physical functioning, role-physical functioning, bodily pain, general health, vitality, social functioning, role-emotional functioning and mental health. RESULTS: The follow-up period of the surveillance group was significantly longer than that of the remaining two groups receiving chemotherapy; however, scale scores were not affected by the duration of follow up in either group. No significant difference was observed in any scale scores between the patients undergoing chemotherapy and those in the surveillance group. In comparison with the general population in the USA, social functioning in both the chemotherapy and surveillance groups was significantly lower, whereas vitality in these two groups was significantly higher. Patients undergoing standard-dose chemotherapy alone had a significantly higher score for mental health than those undergoing high-dose chemotherapy. However, there were no significant differences in the remaining seven scores, irrespective of the type of chemotherapy. CONCLUSIONS: Seven of the eight scale scores of HRQoL were favorable in patients who received chemotherapy or surveillance, and no significant difference was observed between these two groups. Moreover, with the exception of the mental health score, HRQoL was not significantly affected by the type of chemotherapy. Therefore, patients who received chemotherapy, including high-dose chemotherapy with PBSCT, seem to be generally satisfied with their overall HRQoL.     

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.     

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.