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Oncology Aug 2000The prognosis of germ cell tumors treated with chemotherapy depends on the presence of nonseminomatous tumor, clinical parameters based on the tumor volume and site, as... (Clinical Trial)
Clinical Trial
Risk-adapted chemotherapy of germ cell tumors with carboplatin, etoposide and bleomycin for low-risk and cisplatin, etoposide and ifosfamide for high-risk patients. A single-center study.
The prognosis of germ cell tumors treated with chemotherapy depends on the presence of nonseminomatous tumor, clinical parameters based on the tumor volume and site, as well as on the level of the tumor markers AFP, betaHCG and LDH. We report here on the results of a risk-adapted approach to the chemotherapy of germ cell tumors. Patients with low-risk tumors, defined as seminomatous disease and/or nonseminomatous disease with a tumor mass <10 cm, less than 20 lung metastases, no liver, bone, or CNS metastases, and levels of AFP <1,000 IU/ml and betaHCG <10,000 IU/l, were to receive 4 cycles of carboplatin 400 mg/m(2) i.v. day 1, etoposide 120 mg/m(2) i.v. days 1-3 and bleomycin 30 IU i.v. days 1, 8 and 15 during the first 3 cycles (CEB(90)). Patients with high-risk disease were to receive 4 cycles of ifosfamide 1,500 mg/m(2) continuous infusion on days 1-4 together with mesna 1,200 mg/m(2) days 1-5, cisplatin 20 mg/m(2) i.v. days 1-5 and etoposide 100 mg/m(2) i.v. days 1-5 (VIP). Of the 60 patients treated with this risk-adapted approach, 51 had low-risk and 9 had high-risk disease. Forty-five of 51 patiens treated with CEB(90) achieved complete remission (CR), 4 achieved partial remission with marker negativity. Four patients with CR relapsed between 4 to 8 months after the start of chemotherapy. Of the 6 patients failing CEB(90), 3 were treated successfully with surgery or further chemotherapy. With a median follow-up of 52 months, the estimated cause-specific 3-year survival is 93% (95% confidence interval, CI, 80-98%). Seven of 9 high-risk patients treated with VIP achieved a CR and 1 patient relapsed. All 3 patients failing VIP had successful salvage therapy. With a medium follow-up of 63 months all patients remain alive and free of disease. Forty-six patients receiving CEB(90) were retrospectively classified to be in the good prognosis group according to the international germ cell consensus classification. Their estimated 3-year survival was 95% (CI 81-99%). We thus confirm that CEB(90) is a well-tolerated outpatient regimen with good results in good prognosis germ cell tumors. Bleomycin at a cumulative dose of 270 U might contribute substantially to the inferior effect of carboplatin as compared to cisplatin. However, in view of the results of randomized studies favoring cisplatin over carboplatin, it is not recommended to use this regimen outside a clinical trial.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Cisplatin; Etoposide; Follow-Up Studies; Germinoma; Humans; Ifosfamide; Middle Aged; Risk Factors; Treatment Outcome
PubMed: 10971168
DOI: 10.1159/000012146 -
European Urology May 2000In order to reduce therapy-related morbidity in patients with nonseminomatous testicular germ cell tumors in clinical stage IIA/B, we performed a prospective multicenter... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
In order to reduce therapy-related morbidity in patients with nonseminomatous testicular germ cell tumors in clinical stage IIA/B, we performed a prospective multicenter trial comparing the standard retroperitoneal lymph node dissection (RPLND) +2 cycles of chemotherapy (arm A) with 3-4 cycles of primary chemotherapy (arm B).
METHODS
From February 1991 to July 1995, 57 participating centers from Germany and Austria recruited 187 evaluable patients. 109 received primary RPLND and 78 primary chemotherapy. Two different chemotherapies were applied (PEB and CEB as adjuvant or inductive treatment). The quality of life (QoL), therapy-related morbidity, suspected predictive factors (histology and size of metastases), and outcome were assessed.
RESULTS
In arm A, 12% had pathological stage (PS) I, 70% PS II A/B, and 18% PS II C/III. In arm B, 67% achieved complete remission with chemotherapy alone, 33% required a secondary RPLND. After a median follow-up of 36 months, 7% of the patients in arm A and 11% in arm B had relapsed. Two patients died due to complications of chemotherapy. Surgical complications amounted to 12% in arm A and 27% of 26 postchemotherapy RPLNDs (9% in arm B). Loss of ejaculation occurred in 32% in arm A, and 16% in arm B. Acute toxicity of chemotherapy was higher in the group receiving primary chemotherapy.
CONCLUSION
We recommend primary RPLND because adjuvant chemotherapy can be spared in PS I, two cycles of chemotherapy are less toxic than 3 or 4 cycles, the primary operation is associated with less complications than that following chemotherapy and, with modern surgical procedures, ejaculation can be preserved in most of the patients, provided that the operation is carried out by an experienced surgeon. No statistically significant differences in the QoL outcome occurred between the treatment groups, suggesting that chemotherapy alone is not superior to primary or secondary RPLND in this respect.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Cisplatin; Etoposide; Germinoma; Humans; Lymph Node Excision; Male; Neoplasm Staging; Quality of Life; Retroperitoneal Space; Testicular Neoplasms
PubMed: 10765098
DOI: 10.1159/000020197 -
Gynecologic Oncology Jul 1998To evaluate the outcome and the prognosis of patients with ovarian germ cell malignancies who were treated with platinum-based chemotherapy immediately after initial...
PURPOSE
To evaluate the outcome and the prognosis of patients with ovarian germ cell malignancies who were treated with platinum-based chemotherapy immediately after initial surgery.
METHODS
We conducted a retrospective review of patients with ovarian germ cell tumors who were referred for consideration of treatment to the Departments of Medical Oncology participating in the Hellenic Cooperative Oncology Group.
RESULTS
Over a 14-year period 53 patients were included in our study. There were 13 patients with dysgerminoma and 40 patients with nondysgerminomatous tumors. Forty percent of patients underwent complete resection of their tumors. Platinum-based chemotherapy consisted primarily of cisplatin, vinblastine, and bleomycin (PVB) in 9 patients; bleomycin, etoposide, and cisplatin (BEP) in 15 patients; and bleomycin, etoposide, and carboplatin (BEC) in 25 patients. With a median follow-up of 39 months, 5 patients developed progressive disease and died of their tumor and 1 patient died of bleomycin-induced lung toxicity with no evidence of active tumor. The 5-year overall survival was 100% for patients with dysgerminoma and 85% for patients with nondysgerminomatous tumors. Eighty percent of patients with advanced nondysgerminomatous tumors and residual disease after surgery remain disease free.
CONCLUSION
With this study we confirm that patients with ovarian germ cell malignancies have a favorable outcome when treated with platinum-based chemotherapy.
Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Child; Cisplatin; Etoposide; Female; Germinoma; Humans; Middle Aged; Ovarian Neoplasms; Prognosis; Retrospective Studies; Survival Rate; Treatment Outcome; Vinblastine
PubMed: 9698477
DOI: 10.1006/gyno.1998.5047 -
Medical and Pediatric Oncology Apr 1998We report the efficacy and late effects of carboplatin, etoposide, and bleomycin (JEB) for extracranial non-gonadal tumours (GCII, 1989-95) compared with the 5 previous... (Clinical Trial)
Clinical Trial Comparative Study Review
UKCCSG's germ cell tumour (GCT) studies: improving outcome for children with malignant extracranial non-gonadal tumours--carboplatin, etoposide, and bleomycin are effective and less toxic than previous regimens. United Kingdom Children's Cancer Study Group.
BACKGROUND
We report the efficacy and late effects of carboplatin, etoposide, and bleomycin (JEB) for extracranial non-gonadal tumours (GCII, 1989-95) compared with the 5 previous regimens (GCI, 1979-1988) consisting of 3 vincristine, actinomycin, and cyclophosphamide (VAC) and 2 platinum-based protocols.
METHODS AND RESULTS
Median follow-up for 52 patients in the GCI study and 46 in GCII was 105 and 48 months, respectively. For GCI, 5- and 10-year actuarial survival was 63% (95% Confidence interval 50 to 75%) or 72% (57 to 83%) if 6 cases given low-dose VAC were excluded. For GCII, 5-year survival was significantly greater at 95% (83 to 99%), p = 0.01. Event-free survival was 46% at 5 years for GCI (33 to 59%) or 52% excluding the low-dose VAC cases (38 to 66%), while for GCII it was 87% (74 to 94%), p = 0.002. Five-year event-free survival of 21 children given cisplatin, etoposide, and bleomycin (BEP) in GCI was 57% (37 to 76%) compared with 87% (74 to 94%) for 46 given JEB in GCII, P = 0.02. Late effects in 30 evaluable survivors of GCI and 43 GCII included renal impairment in 6 in GCI and 0 in GCII and deafness in 11 and 4, respectively. Among 17 survivors of sacrococcygeal tumours treated in GCI, 4 have neuropathic bladder/bowel and another shortening of a leg. In GCII, 4 of 26 have neuropathic bladder/bowel with lower limb weakness in one.
CONCLUSIONS
We found JEB to be more effective and less toxic than our previous regimens. Some survivors of sacrococcygeal tumours have neurological late effects.
Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Child; Child, Preschool; Cisplatin; Etoposide; Female; Germinoma; Humans; Infant; Male; Prognosis; Recurrence; Survival Analysis; Treatment Outcome
PubMed: 9473756
DOI: 10.1002/(sici)1096-911x(199804)30:4<217::aid-mpo3>3.0.co;2-j -
European Journal of Pediatric Surgery :... Jun 1997To see the impact of cisplatin- and carboplatin-based protocols on survival in malignant sacrococcygeal teratomas (SCT).
AIM OF STUDY
To see the impact of cisplatin- and carboplatin-based protocols on survival in malignant sacrococcygeal teratomas (SCT).
METHODS
Twenty infants and children with malignant SCT were treated at the Hospital for Sick Children, Great Ormond Street, London, over a 16-year period from 1979 to 1994. There were 5 males and 15 females, age ranged from 1 day to 3.5 years (mean 18 months).
RESULTS
Twelve patients (60%) had distant metastasis: 9 lung metastasis, 2 liver involvement, 2 bony metastases, 1 cerebral metastasis and 1 bilateral inguinal lymph node deposits. From 1982 to 1986, patients received the BEP chemotherapy protocol which included cis-platinum, bleomycin and etoposide (VP 16). After 1986, cis-platinum was replaced with carboplatin in the new JEB protocol. Patient 1 did not receive any chemotherapy, Patients 2-4 received varying protocols (2 deaths), Patients 5-8 received the BEP regime (1 death) and Patients 9-20 received JEB (1 death). The first three deaths were due to uncontrolled local disease and/or metastasis, while the latter death was due to bleomycin toxicity. Overall, 9 of 12 (75%) patients with distant metastasis survived as opposed to 7 of 8 (88%) patients with localised disease. Of the 12 patients who received the JEB protocol, 11 (92%) survived, including 7 patients with metastatic disease and 2 with local recurrence. Seven patients (35%) had relapse while on treatment or follow-up, 4 of these are disease-free with further therapy. In 6 of these children, serum AFP rose before there was clinical or radiological evidence of relapse. In 2 other patients, further chemotherapy was recommenced solely on the basis of rising serum AFP, these patients did not subsequently develop overt metastasis.
CONCLUSIONS
We conclude that the treatment of choice for malignant SCT is the JEB regime, to be given for 4 courses or to be continued for 2 courses beyond documented Complete Response (CR). Excision of the primary tumour and coccyx should be done in all cases even if a CR has been documented. Metastases not responding to chemotherapy would need appropriate surgery, radiotherapy is hardly ever needed. An overall cure rate exceeding 90% can be expected.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Cause of Death; Chemotherapy, Adjuvant; Child, Preschool; Cisplatin; Coccyx; Combined Modality Therapy; Etoposide; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Sacrum; Spinal Neoplasms; Survival Rate; Teratoma
PubMed: 9241501
DOI: 10.1055/s-2008-1071078 -
Journal of Clinical Oncology : Official... May 1997This prospective randomized multicenter trial was designed to evaluate the efficacy of carboplatin plus etoposide and bleomycin (CEB) versus cisplatin plus etoposide and... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Randomized trial of bleomycin, etoposide, and cisplatin compared with bleomycin, etoposide, and carboplatin in good-prognosis metastatic nonseminomatous germ cell cancer: a Multiinstitutional Medical Research Council/European Organization for Research and Treatment of Cancer Trial.
PURPOSE
This prospective randomized multicenter trial was designed to evaluate the efficacy of carboplatin plus etoposide and bleomycin (CEB) versus cisplatin plus etoposide and bleomycin (BEP) in first-line chemotherapy of patients with good-risk nonseminomatous germ cell tumors.
PATIENTS AND METHODS
Between September 1989 and May 1993, a total of 598 patients with good-risk nonseminomatous germ cell tumors were randomized to receive four cycles of either BEP or CEB. In each cycle, the etoposide dose was 120 mg/m2 on days 1, 2, and 3, and the bleomycin dose was 30 U on day 2. BEP patients received cisplatin at 20 mg/m2/d on days 1 to 5 or 50 mg/m2 on days 1 and 2. For CEB patients, the carboplatin dose was calculated from the glomerular filtration rate to achieve a serum concentration x time of 5 mg/mL x minutes. Chemotherapy was recycled at 21-day intervals to a total of four cycles.
RESULTS
Of patients assessable for response, 253 of 268 (94.4%) of those allocated to receive BEP achieved a complete response, compared with 227 of 260 (87.3%) allocated to receive CEB (P = .009). There were 30 treatment failures in the 300 patients allocated to BEP and 79 in the 298 allocated to CEB (log-rank chi 2 = 26.9; P < .001), which led to failure-free rates at 1 year of 91% (95% confidence interval [CI], 88% to 94%) and 77% (95% CI, 72% to 82%), respectively. There were 10 deaths in patients allocated to BEP and 27 in patients allocated to CEB (log-rank chi 2 = 8.77; P = .003), which led to 3-year survival rates of 97% (95% CI, 95% to 99%) and 90% (95% CI, 86% to 94%), respectively.
CONCLUSION
With these drug doses and schedules, combination chemotherapy based on carboplatin was inferior to that based on cisplatin. This BEP regimen that contains moderate doses of etoposide and bleomycin is effective in the treatment of patients with good-prognosis metastatic nonseminoma.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Cisplatin; Disease-Free Survival; Etoposide; Germinoma; Humans; Male; Prognosis; Remission Induction; Testicular Neoplasms
PubMed: 9164194
DOI: 10.1200/JCO.1997.15.5.1844 -
Annals of Oncology : Official Journal... Dec 1996Cisplatin-based combination chemotherapy will cure 70% to 80% of patients with metastatic non-seminomatous germ cell tumors but is associated with the possibility of... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
A randomized trial of cisplatin, etoposide and bleomycin (PEB) versus carboplatin, etoposide and bleomycin (CEB) for patients with 'good-risk' metastatic non-seminomatous germ cell tumors.
BACKGROUND
Cisplatin-based combination chemotherapy will cure 70% to 80% of patients with metastatic non-seminomatous germ cell tumors but is associated with the possibility of severe neuro-, oto- and nephro-toxicities. Carboplatin, a cisplatin analogue, is an active drug in testicular cancer with a more favourable spectrum of side effects. In a randomized trial, the German Testicular Cancer Study Group compared a combination regimen of carboplatin, etoposide and bleomycin (CEB) to standard cisplatin, etoposide and bleomycin (PEB) chemotherapy for patients with 'minimal-' and moderate-disease' non-seminomatous germ cell tumors, according to the Indiana University classification.
PATIENTS AND METHODS
PEB was given for three cycles at standard doses (given days 1-5), and the CEB regimen consisted of carboplatin (target AUC of 5 mg/ml x min) on day 1, etoposide 120 mg/m2 on days 1 to 3 and bleomycin 30 mg on days 1, 8 and 15. Four cycles of CEB were given, with the omission of bleomycin in the fourth cycle. Thus, the cumulative doses of etoposide and bleomycin applied in the two treatment arms were comparable. Fifty-four patients were entered on the trial, 29 were treated with PEB and 25 with CEB chemotherapy. Patients were stratified according to disease extent (minimal versus moderate) and the degree of tumor marker elevation. Thirty-two patients (59%) belonged to the group with minimal disease and low markers.
RESULTS
No significant difference in response to chemotherapy was seen between the two arms, with CR rates of 81% for the PEB arm and 76% for CEB treatment. However, more patients treated with CEB (32% versus 13%) have relapsed after therapy, and 4 patients (16%) have died of disease progression after CEP in contrast to 1 (3%) after PEB therapy. The first interim analysis of negative events (relapse, vital tumor at secondary resection, death from disease and therapy-associated death) showed a significantly higher rate after CEB than after PEB therapy, and the trial was terminated early. After a median follow-up of 33 months for all patients, the calculation of negative events is still significantly in favour of PEB-treated patient, particularly since three late relapses > 2 years have been observed in the CEB arm (P = 0.03).
CONCLUSION
This randomized trial demonstrates that even with the use of adequate doses of etoposide and full-dose bleomycin, carboplatin cannot altogether replace cisplatin in patients with testicular cancer. Treatment with the PEB regimen remains the standard approach in patients with 'good-risk' non-seminomatous germ cell tumors.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Cisplatin; Drug Administration Schedule; Etoposide; Germinoma; Humans; Male; Middle Aged; Prognosis; Risk Factors; Testicular Neoplasms
PubMed: 9037359
DOI: 10.1093/oxfordjournals.annonc.a010493 -
Annals of Oncology : Official Journal... Dec 1996
Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Cisplatin; Etoposide; Female; Germinoma; Humans; Male; Ovarian Neoplasms; Randomized Controlled Trials as Topic; Testicular Neoplasms
PubMed: 9037354
DOI: 10.1093/oxfordjournals.annonc.a010521 -
Haematologica 1996Hodgkin's disease (HD) after the age of 65 years is uncommon and there are no published data on chemotherapy regimens devised for elderly HD patients.
BACKGROUND
Hodgkin's disease (HD) after the age of 65 years is uncommon and there are no published data on chemotherapy regimens devised for elderly HD patients.
PATIENTS AND METHODS
From 1990 to 1993, 25 elderly HD patients were treated with the CVP/CEB regimen: chlorambucil 6 mg/sqm p.o. days 1 through 7, vinblastine 6 mg/sqm i.v. on day 1, procarbazine 100 mg/sqm p.o. days 1 through 7, prednisone 30 mg/sqm p.o. days 1 through 7, cyclophosphamide 500 mg./sqm i.v. day 15, etoposide 70 mg/sqm i.v. day 15, bleomycin 10 mg/sqm i.v. day 15. Each course was repeated every 4 weeks. Stage I and II patients were treated with 3 courses followed by involved field radiotherapy, while more advanced stage patients received 6 courses and radiotherapy was limited to bulky areas. The results of the CVP/CEB regimen are retrospectively compared to those of 74 elderly patients treated between 1982 and 1989 and subdivided into the following 2 groups: 32 patients treated according to the same therapy used at that time in younger patients, and 42 patients given alternative low aggressivity or palliative treatment.
RESULTS
CVP/CEB is a well-tolerated regimen, with only 1 (4%) toxic death and 2 (8%) protocol violations/interruptions. The CVP/CEB complete remission rate (73%) compares favorably with our previous groups of patients, mainly because of the lower toxic death rate. However, the CVP/CEB relapse-free survival rate is lower than that of patients treated with more aggressive conventional regimens (47% vs. 77%, p < 0.02). The CVP/CEB overall survival and event-free survival rates are 55% and 32%, respectively, and they are not statistically different from those of patients treated before 1990.
CONCLUSIONS
CVP/CEB is a well-tolerated low toxicity regimen with a high CR rate. The relapse rate is high and event-free survival is comparable to that of patients treated conventionally. Our results suggest the need for individualized treatment criteria for older patients with HD.
Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Cyclophosphamide; Etoposide; Hodgkin Disease; Humans; Prednisone; Treatment Outcome; Vincristine
PubMed: 8952159
DOI: No ID Found -
Journal of the National Cancer Institute Jan 1993
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carboplatin; Cisplatin; Cyclophosphamide; Dactinomycin; Etoposide; Humans; Leukemia, Myeloid, Acute; Male; Mediastinal Neoplasms; Neoplasms, Germ Cell and Embryonal; Neoplasms, Second Primary; Remission Induction; Salvage Therapy; Testicular Neoplasms; Vinblastine
PubMed: 7677936
DOI: 10.1093/jnci/85.1.60