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S Culine

Publications and source records attributed to S Culine.

At least 73 records · Page 4Linked to original sources
PubMed1997

Experience with bleomycin, etoposide, cisplatin (BEP) and alternating cisplatin, cyclophosphamide, doxorubicin (CISCA(II))/vinblastine, bleomycin (VB(IV)) regimens of chemotherapy in poor-risk nonseminomatous germ cell tumors.

Forty poor-risk patients with metastatic nonseminomatous germ cell tumors were treated with a chemotherapy regimen that consisted of either the BEP protocol (bleomycin + etoposide + cisplatin) or the CISCA(II)/VB(IV) regimen (cyclophosphamide + doxorubicin + cisplatin/vinblastine + bleomycin). There was no randomization. Among 17 patients who received the CISCA(II)/VB(IV) protocol, three early deaths, four primary failures, and 10 complete responses were observed. Two relapses and one acute myeloid leukemia were subsequently noted. Nine (53%) of 17 patients remain free of disease 15-38 months after the end of therapy. In the group of patients treated with the BEP regimen, one early death, one primary failure, one toxic death, one partial response, and 19 complete responses were observed. There were eight relapses. Sixteen (70%) of 23 patients remain free of disease 26-52 months after the end of therapy. Myelosuppression and mucositis were clearly more severe with the CISCA(II)/VB(IV) regimen. However, no septic death was registered, whereas one patient died of septic shock after the fourth cycle of BEP. Investigators of the Genitourinary Group of the French Federation of Cancer Centers have now embarked on a prospective randomized trial of BEP versus CISCA(II)/VB(IV) in poor-risk patients.

Adolescent↗
PubMed1997

Phase II study of irinotecan in the treatment of advanced colorectal cancer in chemotherapy-naive patients and patients pretreated with fluorouracil-based chemotherapy.

PURPOSE: To assess the efficacy of irinotecan (CPT-11) in the treatment of advanced colorectal cancer in both chemotherapy-naive and pretreated patients. PATIENTS AND METHODS: Two hundred thirteen patients (aged 18 to 75 years) with metastatic colorectal cancer, World Health Organization (WHO) performance status < or = 2, and life expectancy > or = 3 months were treated with CPT-11 350 mg/m2 every 3 weeks. All 178 patients eligible for efficacy analysis had not received more than one prior fluorouracil (5-FU)-based chemotherapy regimen (adjuvant or palliative) and had adequate hematologic, renal, and hepatic function. RESULTS: Primary tumor sites were the colon (71%) and rectum (28%). Sixty-six percent of the patients had > or = two metastatic sites. Ninety-eight percent of the patients had undergone previous surgery, and 77.5% had received prior chemotherapy. Thirty-two of 178 eligible patients achieved on objective response (four complete responses [CRs] and 28 partial responses [PRs]; response rate, 18%; 95% confidence interval, 12.6% to 24.4%), 65 were stable, and 59 progressed. The response rate was 17.7% in the pretreated group and 18.8% in the chemotherapy-naive group. Within the former subgroup, response rates of 16.1% were reported in patients who were progressive on prior 5-FU chemotherapy and 19.1% in patients who were progressive off such treatment. The median duration of objective response (9.1 months) and median time to achievement of a response (9.3 weeks) did not differ between chemotherapy-naive and pretreated patients. The most frequent adverse events were neutropenia, which developed in 80% of the patients, delayed diarrhea (87%), alopecia (88%), fatigue (81%), and nausea/vomiting (77%). All these adverse events were manageable. Severe (WHO grade 3 or 4) neutropenia was only observed in 18% of the cycles, leukopenia in 11%, delayed diarrhea in 11%, and nausea and vomiting in 3%. Development of simultaneous grade 3 or 4 neutropenia and delayed diarrhea during 4% of the cycles was the safety issue of greatest concern. CONCLUSION: CPT-11 has definite activity in the treatment of advanced metastatic colorectal cancer both in chemotherapy-naive and in pretreated patients who experienced disease progression on 5-FU, which suggests a lack of cross-resistance between CPT-11 and 5-FU. Diarrhea and neutropenia, the major toxicities of CPT-11, contribute to the risk to develop febrile neutropenic sepsis.

Adult↗
PubMed1997

High-Dose Chemotherapy in Adult Solid Tumors and Lymphoproliferative Disorders: The Need for Randomized Trials.

The demonstration of a dose-effect relationship in a wide spectrum of malignancies including solid tumors and lymphoproliferative disorders, along with the development of new techniques of hematopoietic stem cell support, have given rise to a growing interest for high-dose chemotherapy in recent years. Results in more than 3,000 patients included in nonrandomized trials have been reported in the literature. However, only nine randomized trials addressing the issue of the impact of high-dose chemotherapy on survival have been published: three in non-Hodgkin's lymphoma, one in multiple myeloma, two in metastatic breast cancer, one in germ-cell tumors, one in melanoma, and one in small-cell lung cancer. Firm, reliable conclusions can only be drawn from studies conducted in the salvage treatment of non-Hodgkin's lymphoma and in the first-line treatment of multiple myeloma: high-dose chemotherapy used in a consolidation setting after conventional chemotherapy leads to a survival advantage in chemosensitive patients. Promising but not firmly conclusive results were reported in metastatic breast cancer. The results of the sixteen ongoing randomized trials as well as studies addressing the issue of cost-effectiveness will be critical in establishing definite conclusions on the role of high-dose chemotherapy. With the exception of multiple myeloma and relapsed non-Hodgkin's lymphoma, there is no evidence for treating patients with high-dose chemotherapy outside randomized clinical trials.

Journal Article↗
PubMed1997

Are 3 cycles of bleomycin, etoposide and cisplatin or 4 cycles of etoposide and cisplatin equivalent optimal regimens for patients with good risk metastatic germ cell tumors of the testis? The need for a randomized trial.

PURPOSE: Standard chemotherapy for good prognosis metastatic nonseminomatous germ cell tumors of the testis currently includes etoposide and cisplatin. The optimal number of cycles and the need for bleomycin remain matters of debate. Three cycles of bleomycin, etoposide and cisplatin (BEP) or 4 cycles of etoposide and cisplatin are supposed to represent equivalent optimal regimens. MATERIALS AND METHODS: We analyzed the therapeutic outcome of 75 patients with good risk metastatic nonseminomatous germ cell tumor of the testis who were routinely treated at our institute. The chemotherapy regimens consisted of 4 cycles of BEP in 17 patients, 3 cycles of BEP in 23 patients, and 4 cycles of etoposide and cisplatin in 35 patients. RESULTS: All 75 patients achieved a complete or partial response with normal serum tumor markers. After a median followup of 3.5 years (range 2 to 7.5) the overall no evidence of disease rate was 91% (100, 96 and 83% in patients treated with 4 cycles of BEP, 3 cycles of BEP, and 4 cycles of etoposide and cisplatin, respectively). When considering the number of adverse events in each treatment group, that is the number of surgical complete responses or relapses after complete remission, results appeared similar with 3 or 4 cycles of BEP (2 and 3, respectively) but lower in patients who received 4 cycles of etoposide and cisplatin (11 adverse events). Of the 35 patients treated with etoposide and cisplatin 4 (11%) died of disease while only 1 of the 40 (3%) treated with BEP died of disease. CONCLUSIONS: Four cycles of etoposide and cisplatin could yield inferior results compared to 3 cycles of BEP in patients with good risk nonseminomatous germ cell tumor of the testis. Our results highlight the need for a randomized trial addressing the question of therapeutic equivalence between these 2 chemotherapy regimens.

Adolescent↗
PubMed1997

[Primary mediastinal non-seminomatous germ-cell tumors: from clinics to biology].

Primary mediastinal non-seminomatous germ-cell tumors (PMNSGCTs) are rare neoplasms that occur in young male adults. Incidence is evaluated about half that of extra-gonadal GCT. Their treatment is generally based on protocols used for testicular cancer, but with poorer results. Based on our experience of 40 patients with PMNSGCTs and data from the literature, we review here the clinical and biological data of these neoplasms. PMNSGCTs seem to constitute a specific entity, distinct from other GCT by the following criteria: true extra-gonadal origin, high incidence in patients with the Klinefelter's syndrome, over-representation of the yolk-sac component, poorer chemosensitivity and survival compared to other GCT, frequent occurrence of non-treatment related hematological neoplasia. The finding of an isochromosome of the short arm of the chromosome 12 in the leukemic karyotype is one of the strongest argument for a common origin in the yolk-sac component of the PMNSGCTs and their associated leukemia. Treatment of PMNSGCTs is still a challenge and should be conducted by a well-trained medical team.

Adolescent↗
PubMed1997

Evaluation of long-term results of a modified VAB-6 chemotherapy regimen in a cohort of good-risk metastatic non seminomatous germ-cell tumors.

From 1984 to 1988, we conducted at Institut Gustave-Roussy a phase II trial with a modified VAB-6 (mVAB-6) chemotherapy regimen in 50 patients with good prognosis metastatic non seminomatous germ-cell tumors, including 27 patients (54%) with retroperitoneal lymph nodes only. The mVAB-6 combination consisted of vinblastine 4 mg/m2/day at d1, of actinomycin D1 mg/m2/day at d1, of cyclophosphamide 600 mg/m2/day at d1, of cisplatin 120 mg/m2/day at d1 and of bleomycin 20 mg/day from d1 to d3. Four cycles of mVAB-6 were delivered every 4 weeks. A complete response was observed in 46 patients (92%). The other 4 patients achieved a partial response with normal serum tumor markers. Forty-two patients (84%) remain continuously free of disease. Eight relapses subsequently occurred 3 to 60 months after the end of treatment. Overall 45 patients (90%) remain free of disease after a median follow-up of 8 years. The long-term clinical toxicity was minimal. Three patients developed secondary tumors: 2 contralateral non seminomatous germ-cell tumors and 1 pancreatic adenocarcinoma. We conclude that the mVAB-6 regimen yielded excellent results and minimal long-term toxicity in this group of patients with very good-risk metastatic tumors.

Adolescent↗
PubMed1997

[Medical treatment of ovarian malignant germ cell tumors in the adult].

Malignant ovarian germ cell tumors are infrequent neoplasms that usually affect young and otherwise healthy females. The outcome of patients has been significantly improved by the introduction of cisplatin-based chemotherapy. After conservative surgery which both establishes the diagnostic and initiates therapy, the postoperative management should be adapted to histological type as well as to tumor stage. In patients with nonseminomatous germ cell tumors, the standard treatment is a combination of bleomycin, etoposide and cisplatin (BEP protocol). The number of cycles to be given is 3 when surgery is optimal, and 4 in patients with residual or metastatic disease. In patients with pure dysgerminomas, 4 cycles of BEP are the optimal treatment for advanced stages. In early stages, the alternative to chemotherapy (3 cycles of BEP) is radiotherapy, typically given to the ipsilateral hemipelvis and para-aortic nodes. Results are satisfactory with a long-term survival rate ranging from 80 to 100%, and a minimal toxicity yielding a reasonable probability of having normal offspring.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Chemotherapy of germ-cell tumors of poor prognosis and role of intensification with hematological support].

Poor-risk germ-cell tumors are defined by the presence of high serum tumor marker and large tumor burden. The standard treatment of this group of patients is four cycles of a combination of bleomycin, etoposide and cisplatin followed by the surgical exeresis of residual disease. Neither cisplatin dose-intensification nor alternating chemotherapy protocols, high-dose induction protocols and high-dose consolidation regimens have demonstrated better results than the standard chemotherapy regimen. The salvage treatment of germ-cell tumors is a combination of vinblastine, ifosfamide and cisplatin followed by the surgical exeresis of residual disease. The role of high-dose consolidation chemotherapy is studied in an international randomized trial. However high-dose chemotherapy is inactive in refractory disease patients. Innovative trials are developed in this group of patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Desmoplastic small round cell tumors: results of a four-drug chemotherapy regimen in five adult patients.

BACKGROUND: Desmoplastic small round-cell tumor has been identified as a neoplasm with multidirectional immunohistochemical, and molecular features of this tumor sets it apart as a pathologic entity. The optimal treatment remains to be determined. METHODS: Five adult patients were treated according to a uniform first-line chemotherapy program including cisplatin, etoposide, cyclophosphamide, and either doxorubicin or epirubicin. Chemotherapy was delivered after initial surgery in the four patients with intra-abdominal presentation, and at relapse in the fifth patient who had a paratesticular primary tumor. RESULTS: All 4 patients with intra-abdominal disease experienced stability lasting from 4 to 9 months. Only one objective persistent complete response was observed; this was in the patient with a paratesticular primary. No salvage treatment was active in the other four patients who died of progressive disease. CONCLUSIONS: Our experience to a certain degree of chemosensitivity for desmoplastic small round-cell tumors. Despite aggressive treatments, survival rates remain disappointing. Other therapeutic modalities are needed to improve these results.

Adult↗
PubMed1996

Cisplatin and ifosfamide with either vinblastine or etoposide as salvage therapy for refractory or relapsing germ cell tumor patients: the Institut Gustave Roussy experience.

BACKGROUND: Approximately 30% of patients with metastatic germ cell tumors require salvage chemotherapy for recurrent or refractory disease after first-line treatment. The optimal salvage chemotherapy regimen remains to be determined. METHODS: Fifty-four patients with metastatic germ cell tumors who failed to be cured with first-line therapy, were treated with a salvage VIP/VeIP regimen including cisplatin (20 mg/m2/d dl to d5), ifosfamide (1.2 gm/m2/d dl to d5), and either etoposide (75 mg/m2/d dl to d5) or vinblastine (0.11 mg/kg/d dl and d2) for 5 consecutive days every 3 weeks. RESULTS: A complete remission was observed in 24 patients (44%) at completion of VIP/VeIP chemotherapy. In 17 patients (31%), complete remission was reached with chemotherapy alone, whereas four (7%) were rendered tumor-free by resection of the residual inactive tumor. Three patients (6%) became tumor-free by resection of the residual carcinoma. Ten other patients (19%) achieved a partial response, with normalization of serum tumor markers. Eleven of those thirty-four patients additionally received high-dose chemotherapy with hematopoietic stem cell support as consolidation treatment. Twenty patients (37%) were judged to be treatment failures because of either incomplete response (3 patients) or progression of disease (17). Myelotoxicity was severe, but no toxicity deaths were noted. After a median follow-up of 30 months, 23 patients (43%) are alive, 16 of whom (30%) are without evidence of progression of disease. Among patients who received high-dose chemotherapy, the relapse-free survival was 63% compared with 35% for patients who did not receive this consolidation treatment. CONCLUSIONS: Currently available salvage chemotherapy with ifosfamide and cisplatin is predicted to cure approximately 30% of the patients who have failed first-line treatment. Whether high-dose chemotherapy with hematopoietic stem cell support after salvage VIP/VeIP could improve these modest results remains to be confirmed in a randomized study.

Adolescent↗
PubMed1996

Cisplatin-based chemotherapy after retroperitoneal lymph node dissection in patients with pathological stage II nonseminomatous germ cell tumors.

In order to assess the results of cisplatin-based chemotherapy after primary lymph node dissection in patients with pathological stage II nonseminomatous germ cell tumors of the testis, we retrospectively reviewed the long-term outcome of 44 patients who received adjuvant chemotherapy at Institut Gustave Roussy over a 7-year period. Two chemotherapy regimens were sequentially delivered. Twenty-three patients were treated with vinblastine, cyclophosphamide, bleomycin, actinomycin D, and cisplatin (mVAB-6, four cycles), while 21 patients received a combination of etoposide and cisplatin (EP, four cycles). After a median follow-up of 6 years, all patients remain free from progression. The long-term toxicity included retrograde ejaculation in eight patients and severe ototoxicity in two patients. We conclude that four cycles of cisplatin-based chemotherapy for pathological stage II testicular cancer resulted in a 100% cure rate with minimal toxicity.

Adolescent↗
PubMed1996

Is there a role for second-look laparotomy in the management of malignant germ cell tumors of the ovary? Experience at Institut Gustave Roussy.

The last two decades have seen great improvements in the management of patients with germ-cell tumors of the ovary. The initial treatment approach includes conservative surgery and cisplatin-based chemotherapy in most cases. At completion of chemotherapy, the role of second-look surgery remains questionable. We retrospectively analyzed the long-term outcome (median follow-up, 8 years) of 40 patients who received various chemotherapy regimens after primary surgery and focused on the role of second-look surgery. A second-look laparotomy was performed at completion of chemotherapy in 22 patients. Histological findings were no tumor in 13; mature teratoma in 5; immature teratoma in 1; active disease in 3. Six of the latter nine patients had persistent radiologic abnormalities after chemotherapy. All three patients with active disease had elevated serum tumor markers. Five out of the six patients with residual teratoma lesions had a teratoma component in the primary tumor. According to histological findings at second-look surgery, the number of patients without long-term evidence of disease is 12, 5, 1 and 0, respectively. Eighteen patients were not subjected to second-look surgery. One of them had clearly progressive disease and the other 17 experienced a clinical complete response at completion of chemotherapy. All patients but one are alive without evidence of disease. We conclude that second-look surgery is not necessary in patients with elevated serum tumor marker levels and in those patients with neither radiologic abnormality nor teratoma element in the primary tumor. However, we recommend a second-look procedure for the small subset of patients with a teratoma component in the primary tumor and persistent radiologic abnormalities along with normal serum tumor markers at the end of chemotherapy.

Adolescent↗
PubMed1996

Primary treatment in stage II non-seminomatous germ cell tumours of the testis: a matter of scalpel or drug infusion?

The optimal primary treatment of patients with low volume (< or = 5 cm) retroperitoneal metastases remains a matter of debate. Retroperitoneal lymph node dissection (RPLND) is a common practice in North America whereas chemotherapy is a prevailing approach in Europe. In patients with normal serum tumour markers after orchiectomy, primary RPLND appears to be the most appropriate way of staging. In other patients, neither surgery nor chemotherapy are entirely sufficient as monotherapy since approximately one-third of cases for each approach will need the other for achieving optimal results. Treatment decisions are based on cost/benefit and risk/benefit considerations, including relative toxicity and individual patient preference. The treatment of low volume stage II non-seminomatous germ cell tumours (NSGCT) clearly is a matter of scalpel and drug infusion.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

High-dose chemotherapy in germ-cell tumors.

The majority of patients with advanced-stage germ-cell tumor are curable by cisplatin-based chemotherapy, but about 10% of those in the good-risk and 30%-50% in the poor-risk groups will experience relapse. Patients in first relapse have a 60% chance of entering a second complete remission and a 15%-25% probability that it will be durable. Regimens of high-dose chemotherapy with hematopoietic stem-cell support have been developed specifically for this patient population; they are usually based on combinations of etoposide, cyclophosphamide, ifosfamide and, originally, double-dose cisplatin or, nowadays, high-dose carboplatin. The role of high-dose chemotherapy was studied initially in salvage and later in first-line treatment. Four hundred thirty-six patients who received high-dose salvage chemotherapy have been reported, 96 (22%) of whom have obtained long-term complete remissions. Prognostic factors for outcome were disease status (absolute refractory, refractory or sensitive diseases), primary tumor site, response to prior chemotherapy and serum hCG levels prior to high-dose treatment. Patients with no adverse prognostic factors have a greater than 50% chance of cure after high-dose treatment. Patients with refractory disease did not benefit from high-dose chemotherapy. A randomized European trial is ongoing to evaluate prospectively the role of high-dose chemotherapy in comparison to standard ifosfamide-based salvage treatment. In first-line consolidation treatment of poor-risk non-seminomatous germ-cell tumors, the results of phase II trials with carboplatin-based high-dose therapy are in favor of a survival impact when compared to historical controls. A prospective randomized trial is ongoing in the US to study the role of carboplatin-based high-dose consolidation treatment. The only prospective trial comparing a cisplatin-based high-dose treatment to standard chemotherapy failed to demonstrate any survival advantage for the high-dose procedure in this setting. New developments include the use of repeated cycles of high-dose chemotherapy with peripheral blood stem-cell support and the introduction of paclitaxel, a new active drug in this disease, and other non-cross-resistant cytotoxic agents in high-dose combination regimes.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Primary chemotherapy in patients with nonseminomatous germ cell tumors of the testis and biological disease only after orchiectomy.

PURPOSE: We assessed the efficacy of primary chemotherapy in patients with nonseminomatous germ cell tumors of the testis and elevated serum tumor markers as the only evidence of disease after orchiectomy. MATERIALS AND METHODS: We analyzed the outcome of 20 patients with biological disease only who received cisplatin-based (16) or carboplatin-based (4) chemotherapy as primary treatment following orchiectomy. RESULTS: Serum tumor markers returned to normal levels in all 20 patients. One patient required subsequent surgery for recurrent retroperitoneal mature teratoma. Two patients experienced a relapse with active disease, 1 of whom died of progressive germ cell tumor. Of the patients 19 remained free of disease 18 to 116 months after the end of treatment. CONCLUSIONS: Since results with primary retroperitoneal lymph node dissection suggest that elevated serum tumor markers usually reflect systemic metastases rather than retroperitoneal disease, primary chemotherapy seems to be the most appropriate strategy to consider in patients with biological disease only following orchiectomy.

Adolescent↗