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.     

The effect of cisplatin dose and surgical resection in children with malignant germ cell tumors at the sacrococcygeal region: a pediatric intergroup trial (POG 9049/CCG 8882)

PURPOSE: This study was designed to evaluate (1) the efficacy of standard or high-dose cisplatin with etoposide and bleomycin and (2) the role of surgical resection in infants and children with malignant germ cell tumors of the sacrococcygeal region (SCT). METHODS: Seventy-four of 317 children presenting to Pediatric Oncology Group (POG)/Children's Cancer Group (CCG) institutions from 1990 through 1996 with malignant germ cell tumors had malignant SCT. There were 62 girls and 12 boys with a median age of 21 months (range, 3 days to 37 months) and median serum alpha-fetoprotein of 35,500 ng/mL. Twelve had undergone resection of a benign SCT as a newborn. Forty-four (59%) had evidence of metastatic disease at time of diagnosis. Presentation by type (Altman classification) was I, 0; II, 2; III, 30; and IV, 42. The initial procedure was biopsy in 45 and resection in 29. Patients were assigned randomly to receive 4 cycles of chemotherapy with etoposide (E) and bleomycin (B) and either high-dose cisplatin (200 mg/m(2) per cycle; HDP) or standard dose cisplatin (100 mg/m(2) per cycle; P). After completion of chemotherapy, 42 of 45 initially treated with biopsy underwent resection. RESULTS: Overall 4-year survival rate is 90% (SE = 4%) and 4-year event-free survival (EFS) is 84% (SE = 6%). Event-free survival data for subgroups of interest are as follows: 4-yr EFS% (SE) P Values Mets (44) 88 (6).48 No Mets (30) 80 (8) HDP EB (37) 89 (6).21 P EB (37) 78 (7) Initial Resection (29) 90 (7).50 Delayed Resection (42) 83 (7) Complete Resection (49) 90 (5).19 CR/PR Partial Resection (22) 77 (10) Biopsy Only (3) 33 (27).005 (3 way) CONCLUSIONS: (1) The current survival rate of malignant sacrococcygeal tumors is excellent even with metastases. (2) Delayed surgical resection is not associated with an adverse outcome. (3) In this subset the treatment comparison was inconclusive however, followed the trend in the overall study of more than 300 children in which the high-dose cisplatin group had superior EFS (P<.05).     

Prognostic analysis of Japanese men with metastatic germ cell tumors showing favorable response to bleomycin, etoposide and cisplatin as first-line chemotherapy

The objective of this study was to evaluate the efficacy of first-line bleomycin, etoposide and cisplatin (BEP) chemotherapy in Japanese patients with metastatic germ cell tumors (GCTs). Between 1996 and 2006, 88 male patients with metastatic GCTs were treated with first-line BEP at our institution. Of these 88, 47 (16, seminoma; 31, nonseminoma), who did not receive high-dose chemotherapy following BEP because of the normalization of serum tumor markers, were included in this study. The primary site was the testis in 42 patients, retroperitoneum in 3, and mediastinum in 2. The full-dose regimen used for BEP consisted of cisplatin 20 mg/m2 on days 1 to 5, etoposide 100 mg/m2 on days 1 to 5, and bleomycin on days 2, 9 and 16. Therapeutic outcome was assessed according to several clinicopathological parameters. Following 2 to 4 cycles of BEP (median, 4 cycles), alpha-fetoprotein, beta-human chorionic gonadotropin and lactate dehydrogenase were normalized in all 47 patients. Eighteen patients (38.3%) achieved a complete response (CR) after BEP alone, while BEP resulted in a partial response and stable disease in the remaining 23 (48.9%) and 6 (12.8%), respectively. In addition, surgical resection of the residual tumors following BEP was performed in 15 patients, of whom 12 (80.0%) and 3 (20.0%) achieved pathological and surgical CR, respectively. At a median follow-up of 27 months, all patients were alive; however, disease recurrence occurred in 5 (seminoma, 1; nonseminoma, 4), and all these 5 were subsequently treated with high-dose chemotherapy as salvage therapy. In this series, 1-, 3- and 5-year recurrence-free survival rates were 95.0, 91.4 and 79.2%, respectively, and, there was no significant difference in recurrence-free survival between patients with seminoma and those with nonseminoma. These findings suggested that patients with metastatic GCTs, regardless of histological subtype (i.e., seminoma or nonseminoma), who showed favorable response to first-line BEP chemotherapy, could achieve an excellent prognostic outcome.     

Salvage chemotherapy with methotrexate,etoposide and actinomycin D in men with metastatic nonseminomatous germ cell tumors with a choriocarcinoma component: A preliminary report

The objective of the present study was to assess the use of salvage chemotherapy using methotrexate, etoposide and actinomycin D (MEA) in men with nonseminomatous germ cell tumor (NSGCT) with a choriocarcinoma component. Nine patients were included. They had initially received bleomycin, etoposide and cisplatin, and high‐dose ifosfamide, carboplatin and etoposide as induction chemotherapies. However, they failed to achieve the normalization of β‐human chorionic gonadotropin (β‐HCG). Therefore, MEA therapy (methotrexate: 450 mg/body on day 1, actinomycin D: 0.5 mg/body on days 1–5, etoposide: 100 mg/body on days 1–5) was subsequently administered. After MEA therapy (median: 3 cycles), serum β‐HCG was normalized in five of the nine patients. Of these five, three achieved long‐term disease‐free survival and one died of disease unrelated to NSGCT, whereas the remaining patient developed disease recurrence and died of disease progression. All four patients who failed to achieve the normalization of β‐HCG died of disease progression. Although several severe toxicities greater than grade 3, which were mainly associated with bone marrow suppression, occurred in all patients, there was no treatment‐related death. Considering the current outcomes, MEA regimen could be an attractive option as a salvage chemotherapy for metastatic NSGCT patients with a choriocarcinoma component showing resistance to intensive conventional chemotherapies.     

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.     

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.     

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.     

Efficient carboplatin single therapy in a mouse model of human testicular nonseminomatous germ cell tumor.

PURPOSE: Cisplatin based combination therapy has shown excellent clinical results in patients with testicular nonseminomatous germ cell tumor but chemotherapy induced morbidity and reduced patient compliance are limiting factors in this regimen. To decrease cisplatin based combination therapy induced morbidity we examined carboplatin versus etoposide single therapy in an animal model. MATERIALS AND METHODS: A total of 180 SCID mice bearing testicular nonseminomatous germ cell tumor xenografts received 120 mg./kg. carboplatin as a single cycle, 60 or 30 mg./kg. carboplatin cycled twice, 80, 50 or 30 mg./kg. etoposide cycled twice, or Ringer solution as the control. An additional 20 sham treated and 20 untreated mice also served as controls. Histological and immunocytochemical testing, in vivo microscopy, vascular corrosion casting, serum tumor markers, complete blood count and real-time polymerase chain reaction were used to monitor therapy efficacy. RESULTS: Carboplatin at 60 mg./kg. cycled twice eradicated the tumor and significantly reduced vascular density and vascular endothelial growth factor-A messenger RNA (p <0.05). Elevated tumor markers returned to baseline after carboplatin administration. Therapy was well tolerated, resulting thrombocytopenia disappeared 6 weeks after therapy and the animals were tumor-free 6 months after treatment. Although 120 mg./kg. carboplatin eradicated the tumor, it resulted in extensive mortality and morbidity. Single treatment 30, 50 and 80 mg./kg. etoposide failed. CONCLUSIONS: Carboplatin single therapy was highly effective in our nonseminomatous germ cell tumor model and it may be examined in future clinical trials in patients with high risk stage I nonseminomatous germ cell cancer for reducing cisplatin based combination therapy induced morbidity. Vascular density and vascular endothelial growth factor messenger RNA were elevated in our animal model and deserve further study in nonseminomatous germ cell tumor cases as potential risk factors.     

Does the substitution of cisplatin in a standard four drug regimen improve survival in small cell carcinoma of the lung? A comparison of two chemotherapy regimens.

Ninety five patients with small cell carcinoma of the lung were randomly assigned to one of two chemotherapy regimens (VACE or CVACE), each consisting of six cycles at three week intervals. The VACE regimen consisted of six cycles of vincristine 1.2 mg/m2, doxorubicin 40 mg/m2, and cyclophosphamide 700 mg/m2 on day 1 plus etoposide 110 mg/m2 daily for three days. The CVACE regimen was identical to the VACE regimen for cycles 3 and 4; cycles 1, 2, 4, and 6 consisted of etoposide 110 mg/m2 for three days plus cisplatin 100 mg/m2 with mannitol diuresis on the second day. Forty eight patients received VACE and 47 CVACE. Side effects resulted in withdrawal of four patients receiving VACE and six receiving CVACE. Three deaths were attributed to VACE and one to CVACE. Median survival did not differ between the two treatments overall, though there was a small increase in median survival in partial responders receiving CVACE. It is concluded that replacing four of the six cycles of VACE (vincristine, doxorubicin, cyclophosphamide, and etoposide) with etoposide and cisplatin conferred no overall advantage.     

Treatment results of VIP (etoposide, ifosfamide and cisplatin) chemotherapy as a first-line therapy in metastatic germ cell tumors

PURPOSE: We investigated the effectiveness and toxicity of VIP therapy as a first-line chemotherapy for patients with metastatic germ cell tumor. PATIENTS AND METHODS: From March 1994 to October 1997, we treated 16 patients with VIP therapy consisting of etoposide (100 mg/m2), ifosfamide, (1.2 g/m2) and cisplatin (20 mg/m2), all of which were generally given daily for 5 consecutive days every 3 weeks. Of the 16 patients, 6 were classified into a good, 5 into an intermediate, and 5 into a poor prognostic group according to the International Germ Cell Consensus Classification. RESULTS: Thirteen patients (81%) achieved complete response with VIP alone or VIP plus surgery. Three-year survival rate was 100% in good and intermediate prognostic group, while 40% in poor prognostic group. Although all patients had Grade 3 or higher myelosuppression, the treatment was well tolerated and no patient died of treatment-related complications. CONCLUSIONS: VIP appears to be an effective and safe regimen as an induction chemotherapy for good and intermediate risk patients with germ cell tumor. However, more intensive regimen may be necessary for poor-risk patients.     

The role of neoadjuvant radiochemotherapy using low-dose fraction cisplatin and 5-fluorouracil in patients with carcinoma of the esophagus

OBJECTIVE: We clarified the role of neoadjuvant radiochemotherapy in patients with carcinoma of the esophagus and compared it to neoadjuvant chemotherapy. METHODS: We retrospectively examined 40 patients diagnosed with advanced thoracic esophageal carcinoma who underwent neoadjuvant therapy followed by esophagectomy between 1993 and 1999. We divided them into 2 groups: radiochemotherapy (17) and chemotherapy (23). Radiochemotherapy patients underwent 40 Gy radiation and low-dose fraction cisplatin (7 mg/body/day, 5 days a week x 4 weeks) and 5-fluorouracil (350 mg/body/day x 28 days). Chemotherapy patients received high-dose fraction cisplatin/5-fluorouracil involving 2 courses of cisplatin (70 mg/m2/day on day 1) and 5-fluorouracil (700 mg/m2/day on days 1-5). RESULTS: Complete pathological response was 17.6% in the radiochemotherapy group and 0% in the chemotherapy group respectively. No hospital mortality occurred in the radiochemotherapy group, and 1 of the 23 chemotherapy patients died in the hospital due to postoperative complications. The incidence of residual tumors was significantly higher in the chemotherapy group (34.8%) than in the radiochemotherapy group (0%). Actuarial survival in the radiochemotherapy group at 1 year was 80.2% and at 3 years 53.5%. Actuarial survival in the chemotherapy group at 1 year was 56.5% and at 3 years 30.4%. CONCLUSIONS: Histological effectiveness was greater in patients treated with preoperative radiochemotherapy than those treated with preoperative chemotherapy. The combination of radiation and low-dose fraction CDDP/5-FU thus is first choice in neoadjuvant radiochemotherapy for the advanced esophageal carcinoma.     

Improved survival rates in children over 1 year of age with stage III or IV neuroblastoma following an intensive chemotherapeutic regimen

Combined chemotherapeutic regimens of (1) cyclophosphamide (40 mg/kg x two days), (2) cisplatinum (20 mg/m2 x five days) plus VM-26 (100 mg/m2), and (3) Adriamycin (60 mg/m2) plus DTIC (250 mg/m2 x five days) were prescribed for 42 Japanese children greater than 1 year of age with stage III or IV neuroblastoma. The protocol was separated into three forms (A, B, and C) from the combination pattern of three such high-dose courses. The cumulative survival rates for those with stages III and IV 48 months after initiation of therapy were 76.2% and 20.1%, respectively, and the overall rate was 36.7%. The tumor disappeared during the course of treatment in 25 of 42 children (59.5%). The 48-month survival rate was superior in patients greater than 5 years of age than younger patients (P less than .01). Even in patients with a tumor originating in the suprarenal region, the 48-month survival rate was 30.5%. Among 12 patients in whom the N-myc oncogene was measured, one of five with one to ten copies of amplification died, whereas all seven with greater than ten copies died or had a recurrence. Thus, the present chemotherapeutic regimens, in particular alternate administration of each high-dose course, considerably improved the survival of patients with stage III neuroblastoma. More aggressive protocols are needed for those with stage IV neuroblastoma who are greater than 1 year of age, particularly in those with an amplified N-myc oncogene.     

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.     

Phase II trial of postoperative adjuvant cisplatin and etoposide in patients with completely resected stage I-IIIa small cell lung cancer: the Japan Clinical Oncology Lung Cancer Study Group Trial (JCOG9101)

OBJECTIVE: Indications for surgical intervention for very limited small cell lung cancer have not yet been determined. The objective of this study is to determine whether resection followed by cisplatin and etoposide is feasible. METHODS: From September 1991 through December 1996, 62 patients with completely resected small cell lung cancer who were less than 76 years of age from 17 centers were entered in the trial. Of 62 patients, 61 were eligible, with a median follow-up of 65 months. Chemotherapy consisted of 4 cycles of cisplatin (100 mg/m 2 , day 1) and etoposide (100 mg/m 2 , days 1-3). There were 49 (80%) male patients, 44 with clinical stage I disease, 10 with stage II disease, and 6 with stage IIIa disease. RESULTS: Forty-two (69%) patients received 4 cycles of cisplatin and etoposide. No treatment-associated mortality was noted. Median survival time was not reached in patients with pathologic stage I disease, was 449 days in patients with stage II disease, and was 712 days in patients with stage IIIa disease. Three-year survival was 61% overall, 68% in patients with clinical stage I disease, 56% in patients with stage II disease, and 13% in patients with stage IIIa disease ( P = .02). Recurrence was noted in 26 (43%) patients overall. Local failure was noted in 6 (10%) patients. Locoregional recurrence tends to be found more frequently in patients with stage IIIA disease. Distant failure was found in 21 (34%) patients overall. Brain metastasis was found in 15% of the patients. CONCLUSION: Major lung resection followed by postoperative cisplatin and etoposide is feasible, with a favorable survival profile. Because nodal metastasis appears to be a major prognostic factor, preoperative evaluation of nodal status remains a major concern.     

Secondary leukemia following ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer

Secondary leukemia following chemotherapy or radiotherapy for mediastinal germ cell tumors in a well-described entity. It also may occur in patients with testicular germ cell tumors. We report a case of secondary leukemia occurring in a 31-year-old man who received ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation (PBSCT) for a refractory testicular cancer (pathology; Seminoma, Embryonal carcinoma, Yolk sac tumor, Choriocarcinoma) with IIIB2 under Japanese classification, poor-risk group under Indiana classification. The initial levels of serum LDH, AFP and beta-HCG were high at 959 IU/l, 1,452 ng/ml and 800 ng/ml. He received total 11 cycles of systemic chemotherapy (2 cycles of PVB regimen, 4 cycles of PEB regimen, 3 cycles of VIP regimen and 2 cycles of ultra high-dose chemotherapy with PBSCT for pulmonary and para-aortic lymph node metastasis following his initial orchiectomy. The total amount of etoposide (VP-16), cisplatin (CDDP), carboplatin (CBDCA) and ifosfamide (IFM), this patient received was 7,225 mg/m2, 1,510 mg/m2 1,750 mg/m2, and 50.5 g. He has survived with CR of disease. Severe and persistent pancytopenia developed 25 months after his initial orchiectomy. Bone marrow examination showed AML (M2 with eosinophilia) under French-America-British (FAB) classification. Therefore, he was diagnosed as secondary leukemia following high-dose chemotherapy. He received total 6 cycles of systematic chemotherapy for the secondary leukemia in the internal department. He is planing to have bone marrow transplantation. To our knowledge, this is the first reported case in the literature relevant to secondary leukemia following ultra high-dose chemotherapy with PBSCT in testicular tumor in Japan.     

Chemotherapy in hemodialysis patient with metastatic testicular cancer; pharmacokinetics of etoposide and cisplatin

The pharmacokinetics of intravenously administrated cisplatin and etoposide were studied in a patient with seminoma (stage IIIA) receiving hemodialysis for chronic renal failure. The treatment schedule was as follows: 7 mg/m2 of cisplatin at day 1, 3, 5; 14 mg/m2 of cisplatin at day 2, 4; 70 mg/m2 of etoposide at day 1-5; hemodialysis at day 2, 4. After the treatment myelosuppression was very strong. So the patient were received another treatment of smaller doses of cisplatin and etoposide in three courses. The other schedule was as follows: 14 mg/m2 of cisplatin at day 1, 3, 5; 35 mg/m2 of etoposide at day 1-5; hemodialysis at day 1, 3, 5. The area under the blood concentration-time curve (AUC) of free-cisplatin was 6.82 micrograms.hr/ml in first course, 4.07 micrograms.hr/ml in second course. The peak concentration of peripheral blood free-cisplatin was 0.58 microgram/ml in first course, 0.43 microgram/ml in second course. The AUC of etoposide was 241.9 micrograms.hr/ml in first course, 216.9 micrograms.hr/ml in second course. After treatment CR was observed and there was no recurrence for five years. In conclusion, it was considered that cisplatin and etoposide could be given to the patient receiving hemodialysis for chronic renal failure and smaller doses should be given to prevent side effects.     

Long-term followup results of 1 cycle of adjuvant bleomycin, etoposide, and cisplatin chemotherapy for high risk clinical Stage I nonseminomatous germ cell tumors of the testis Westermann DH, Schefer H, Thalmann GN, Karamitopoulou-Diamantis E, Fey MF, Studer UE, Department of Urology, University of Bern, Bern, Switzerland

PURPOSE: We evaluated the long-term outcome after 1 cycle of adjuvant modified bleomycin, etoposide, and cisplatin chemotherapy in patients who underwent orchiectomy for high risk clinical Stage I nonseminomatous germ cell tumor of the testis. MATERIALS AND METHODS: Between 1995 and 1999, a consecutive series of 44 patients underwent orchiectomy for clinical Stage I nonseminomatous germ cell tumor of the testis, followed by a single postoperative cycle of adjuvant modified bleomycin, etoposide, and cisplatin for vascular or lymphatic tumor invasion, and/or a predominance (50% or greater) of embryonal carcinoma. RESULTS: Four of the 44 patients were excluded from analysis. Of the patients, 35 had no evidence of disease at a median followup of 99 months (range 60-134). One patient with progression after 13 months showed complete remission after 3 cycles of salvage bleomycin, etoposide, and cisplatin chemotherapy but he died of pneumonia 4 weeks after the third course. Two patients underwent orchiectomy for contralateral testis cancer at 18 and 42 months, respectively, followed by an additional 3 cycles of adjuvant chemotherapy. They remained relapse-free for 4 and 92 months, respectively. The former patient was lost to follow-up after 4 months. Two other patients were disease-free at 10 and 31 months, respectively, and were lost to follow-up thereafter. Late side effects were tinnitus in 3 patients and involuntary childlessness in 3, of whom 2 had cryptorchidism of the contralateral testis. Nine patients fathered children. CONCLUSIONS: One cycle of bleomycin, etoposide, and cisplatin effectively decreases the risk of relapse in patients with high risk Stage I nonseminomatous germ cell tumor of the testis. It has minimal side effects and can be a valuable alternative to retroperitoneal lymph node dissection.     

Disseminated testicular cancer with bulky disease: results of a phase-II study with cisplatin ultra high dose/VP-16/bleomycin

This is a preliminary analysis of the AIO-Testicular Tumour Study Group trial in patients with disseminated bulky testicular cancer. Treatment plan: cisplatin 35 mg/m2 days 1-5, VP-16 120 mg/m2 days 1-5 (two daily divided doses), bleomycin 15 mg/m2 days 1, 8, 15. Of 98 patients at present evaluable 63% had complete remission or have no evidence of disease (CR/NED), 30% had partial remission (PR) and 7% had no change or progressive disease (NC/P). Relapse-free survival is 93% for the CR/NED group after a median follow up of 2.2 years: the overall survival for the entire patient population is 70%. Toxicity included predominantly granulocytopenic fever and infection with septicaemia, thrombocytopenia, nausea, vomiting, neurotoxicity and lung toxicity, with 7% fatal toxicity. A prospective randomized trial is warranted to evaluate the apparent superior activity of ultra high dose cisplatin in combination with VP-16 and bleomycin.     

Peripheral blood stem cell harvest for patients with germ cell tumors

From January 1996 to December 1999, fifteen patients with germ cell tumors underwent peripheral blood stem cell harvest during 15 courses of bleomycin, etoposide, cisplatin (BEP), 4 courses of etoposide, ifosfamide, cisplatin (VIP) and 3 courses of high-dose etoposide mobilization at Nagoya University Hospital. We performed 29 aphereses during BEP, eight during VIP, and six during high-dose etoposide. Although we were able to harvest 4.4 x 10(6)/kg of median CD34 positive cells per apheresis during BEP, the number of stem cells (more than 4 x 10(6)/kg of CD34 positive cells), which are needed for tandem high-dose chemotherapy, could not be obtained during four courses of BEP. For three patients in whom white blood cell counts at nadir were 2,000/microL or more, however, the required number of CD34 positive cells were harvested. VIP provided only 1.7 x 10(6)/kg of median CD34 positive cells per apheresis, while, 7.3 x 10(6)/kg of CD34 positive cells were harvested during high-dose etoposide mobilization. The dose of G-CSF was a significant factor for the number of CD34 positive cells harvested during BEP (p = 0.02); however, there might be some relationship between the harvest and the number of the peripheral white blood cells on the day of apheresis (p = 0.08), the day to start G-CSF (p = 0.13), or the day to initiate apheresis (p = 0.27). Based on our experience, it is recommended that 5 micrograms/kg of G-CSF should be started from the 14th or 15th day of BEP until the last apheresis and that aphereses should be performed between the 19th and 21st day, especially at the days when the peripheral white blood cell count increases beyond 10,000/microL.     

Toxicity of two cisplatin-based radiochemotherapy regimens for the treatment of patients with stage III/IV head and neck cancer

BACKGROUND: This nonrandomized study compared 2 radiochemotherapy regimens for toxicity in 128 patients with stage III/IV head and neck cancer. METHODS: Patients received conventionally fractionated radiotherapy. The total dose to primary tumor and involved lymph nodes did depend on preceding surgery. Patients received 66 to 70 Gy if surgery was not performed, 60 to 66 Gy after R0 resection, 66 Gy after R1 resection, and 70 to 72 Gy after R2 resection. Concurrent chemotherapy consisted of 3 courses cisplatin (100 mg/m(2)/d1,22,43) (group A, N = 61) or 2 courses cisplatin (20 mg/m(2)/d1-5 + 29-33)/5-fluorouracil (5-FU) (600 mg/m(2)/d1-5 + 29-33) (group B, N = 67). RESULTS: Acute toxicity was more severe in group A, especially nausea/vomiting (p = .002), nephrotoxicity (p = .001), ototoxicity (p = .034), and hematotoxicity (p = .049). Forty-eight percent of group A and 10% of group B patients could not complete chemotherapy due to toxicity (p = .018). Late toxicity was similar (p = .99). CONCLUSION: Two courses of fractionated cisplatin (20 mg/m(2)/d) and 5-FU were associated with significantly less acute toxicity than were 3 courses cisplatin (100 mg/m(2)/d).