Ifosfamide is an active drug in Wilms' tumor: a phase II study conducted by the French Society of Pediatric Oncology.

Twenty-one patients with advanced Wilms' tumor entered a phase II study with high-dose ifosfamide (3 g/m2 over two days every 15 days). Mesna and hyperhydration were associated with minimal bladder toxicity. After two courses, five partial responses and six complete responses were observed. Ten patients did not respond. The median duration of response was 2 months (range, 1 to 7). Therapy was delayed because of leukopenia for 1 or 2 weeks in only three cases. Fever and infection were not observed. Seven patients presented with hematuria, three of whom were among the 17 patients coadministered mesna, which did not interfere with subsequent therapy.

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Etoposide and carboplatin in neuroblastoma: a French Society of Pediatric Oncology phase II study.

Journal of Clinical Oncology ◽

10.1200/jco.1992.10.10.1592 ◽

1992 ◽

Vol 10 (10) ◽

pp. 1592-1601 ◽

Cited By ~ 41

Author(s):

D Frappaz ◽

J Michon ◽

O Hartmann ◽

E Bouffet ◽

O Lejars ◽

...

Keyword(s):

Phase Ii ◽

Pediatric Oncology ◽

Phase Ii Study ◽

World Health ◽

High Dose ◽

Hematologic Toxicity ◽

French Society ◽

Who Grade ◽

The Status ◽

Health Organization

PURPOSE A phase II study of etoposide (VP 16) and carboplatin (CBDCA) was performed in patients with metastatic neuroblastoma (NB). The aim of the study was to find an alternative treatment for induction with different toxicities than the VP 16/cisplatin (CDDP) combination. PATIENTS AND METHODS Forty-seven patients who were from 6 months to 16 years of age, with either relapsed (29) or primary resistant (18) NB, were included in a cooperative multicenter phase II study of the French Society of Pediatric Oncology (SFOP). The schedule consisted of 5 consecutive days of VP 16 100 mg/m2/d and CBDCA 160 mg/m2/d. RESULTS The response rate for the 39 assessable patients was 43%; there were four complete remissions and 13 partial remissions. Neither the status of the patients nor the total dose of CDDP that was received previously influenced response. Hematologic toxicity was marked and caused considerable delay between courses (median interval, 39 days). In these heavily pretreated patients, 16% had a more than 50% decrease in creatinine clearance and a 22% World Health Organization (WHO) grade 2 ototoxicity. CONCLUSION This VP 16/CBDCA combination deserves further evaluation for efficacy and toxicity in newly diagnosed patients, and the combination of both drugs should be considered for high-dose therapy with bone marrow transplantation.

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A phase II study of high-dose cisplatin and VP-16 in neuroblastoma: a report from the Société Française d'Oncologie Pédiatrique.

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.6.941 ◽

1987 ◽

Vol 5 (6) ◽

pp. 941-950 ◽

Cited By ~ 43

Author(s):

T Philip ◽

R Ghalie ◽

R Pinkerton ◽

J M Zucker ◽

J L Bernard ◽

...

Keyword(s):

Hearing Loss ◽

Phase Ii ◽

Phase Ii Study ◽

Bone Marrow Involvement ◽

Stage Iv ◽

Observation Time ◽

Phase Iii ◽

High Dose ◽

Initial Stage ◽

Duration Of Response

Forty-seven children or adolescents with initial stage IV (42 patients) or stage III (five) advanced neuroblastoma (12 were progressing after relapse and 35 had never reached complete remission [CR] after conventional therapy) were included in a phase II study of the combination of high-dose VP-16 (100 mg/m2/d X 5) and high-dose cisplatin (CDDP) (40 mg/m2/d X 5). Twenty patients had received prior CDDP therapy (total dose, 100 to 640 mg/m2; median, 320 mg/m2) and 38 of 47 had bone marrow involvement when included in the study. The overall response rate was 55%, with 22% CR. Duration of response was 5 to 18 months, with a median of 10 months. Eight patients are still disease free, with a median observation time of 13 months, but all had received additional therapy after two courses of this regimen. Gastrointestinal toxicity was frequent but tolerable. Myelosuppression was severe but of brief duration, ie, nadir of neutrophils was observed at day 15 with 95% of the patients recovering a normal count before day 28, and nadir of platelet count was at day 17 with only two severe and reversible episodes of bleeding. The overall incidence of sepsis was 8% (seven of 92 courses), with no death related to infection. No acute renal failure was observed after two courses, and only three of 47 children experienced a clear reduction of renal function. After two courses, only two children showed a hearing loss in the 1,000 to 2,000 Hz range, although hearing loss above the 2,000 Hz level was frequently encountered. It is concluded that high-dose VP-16 and CDDP is an effective regimen in advanced neuroblastoma with acceptable toxicity. Phase III studies are needed in previously untreated patients. J Clin Oncol 5:941-950.

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Etoposide and carboplatin: a highly effective combination in relapsed or refractory Wilms' tumor--a phase II study by the French Society of Pediatric Oncology.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.5.931 ◽

1994 ◽

Vol 12 (5) ◽

pp. 931-936 ◽

Cited By ~ 48

Author(s):

F Pein ◽

M F Tournade ◽

J M Zucker ◽

M Brunat-Mentigny ◽

A Deville ◽

...

Keyword(s):

Phase Ii ◽

Phase Ii Study ◽

Wilms Tumor ◽

Complete Response ◽

Hematologic Toxicity ◽

French Society ◽

Effective Combination ◽

Major Toxicity ◽

The Cost ◽

Grade Iii

PURPOSE Since we had previously demonstrated encouraging efficacy of etoposide in patients with relapsed or refractory Wilms' tumor (WT), the likely synergism between etoposide and platinum compounds prompted us to conduct a phase II study of a combination with carboplatin. PATIENTS AND METHODS Twenty-six relapsed or refractory WT patients were included in a phase II study of two courses of combination etoposide 100 mg/m2/d for 5 days and carboplatin 160 mg/m2/d for 5 days, with a 21-day interval between the two courses. Initial stages were I (n = 2), II (n = 8), III (n = 6), IV (n = 6), V (n = 3), and unknown (n = 1). Sites of diseases were lung(s) (11 patients), abdomen-pelvis or liver or primary tumor (six patients), and multiple (eight patients). Histology was unfavorable in three of 26 patients. RESULTS Complete response (CR) was documented in eight patients and partial remission (PR) in 11 (overall response rate, 73%). Stable disease (SD) was observed in five patients and progressive disease (PD) in two. Thrombocytopenia (grade IV) was the major toxicity, and platelet transfusions were required in all but two patients. Grade III anemia and grade III to IV neutropenia were seen in 19 and 23, respectively, of 25 assessable first courses. Venoocclusive disease of the liver was fatal in one child who had undergone irradiation to the whole abdomen, 8 weeks before study. CONCLUSION Combination etoposide and carboplatin has impressive activity in refractory or relapsed WT at the cost of high-grade hematologic toxicity, especially thrombocytopenia. It is of great interest in second-line therapy, since eight of 26 patients are still alive in continuous CR (median follow-up duration, 40 months; range, 24 to 56). This combination deserves further investigation as first-line or consolidation treatment.

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Phase II study of ifosfamide in childhood brain tumors: A report by the French society of pediatric oncology (SFOP)

Medical and Pediatric Oncology ◽

10.1002/mpo.2950210110 ◽

1993 ◽

Vol 21 (1) ◽

pp. 49-53 ◽

Cited By ~ 28

Author(s):

Pascal Chastagner ◽

Danièle Sommelet-Olive ◽

Chantal Kalifa ◽

Maud Brunat-Mentigny ◽

Jean-Michel Zucker ◽

...

Keyword(s):

Brain Tumors ◽

Phase Ii ◽

Pediatric Oncology ◽

Phase Ii Study ◽

French Society ◽

Childhood Brain Tumors

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Carboplatin and VP 16 in medulloblastoma: A phase II study of the French Society of Pediatric Oncology (sfop)

Medical and Pediatric Oncology ◽

10.1002/mpo.2950230506 ◽

1994 ◽

Vol 23 (5) ◽

pp. 422-427 ◽

Cited By ~ 41

Author(s):

Jean Claude Gentet ◽

François Doz ◽

Eric Bouffet ◽

Dominique Plantaz ◽

Henri Roché ◽

...

Keyword(s):

Phase Ii ◽

Pediatric Oncology ◽

Phase Ii Study ◽

French Society

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High-dose melphalan, etoposide, and carboplatin followed by autologous stem-cell rescue in pediatric high-risk recurrent Wilms' tumor: a French Society of Pediatric Oncology study.

Journal of Clinical Oncology ◽

10.1200/jco.1998.16.10.3295 ◽

1998 ◽

Vol 16 (10) ◽

pp. 3295-3301 ◽

Cited By ~ 79

Author(s):

F Pein ◽

J Michon ◽

D Valteau-Couanet ◽

E Quintana ◽

D Frappaz ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Pediatric Oncology ◽

Wilms Tumor ◽

Disease Free Survival ◽

Stage Iv ◽

High Dose ◽

French Society ◽

Time Curve ◽

Disease Free

PURPOSE The three-drug combination of melphalan (M), etoposide (E), and carboplatin (C) followed by autologous stem-cell (ASC) rescue has been evaluated prospectively by the French Society of Pediatric Oncology (SFOP) in pediatric high-risk recurrent (HRR) Wilms' tumor (WT) patients with chemotherapy-responsive disease. PATIENTS AND METHODS From October 1988 to October 1994, 29 patients with HRR WT were treated in nine SFOP centers. Two additional patients with stage IV anaplastic WT were consolidated in first complete response (CR) with the same regimen and have been studied separately. The regimen consisted of M 180 mg/m2 for 1 day, E 200 mg/m2/d for 5 days, and C at a daily targeted area under the concentration-time curve (AUC) of 4 mg x min/mL for 5 days. ASCs were reinfused 48 hours after M. RESULTS Twelve of 28 assessable patients with HRR WT are still in continuous CR at a median of 48.5 months (range, 36 to 96) after consolidation. Disease-free survival (DFS) and overall survival (OS) estimated by the Kaplan-Meier method at 3 years were 50%+/-17% and 60%+/-18%, respectively. Sixteen patients relapsed at a median of 8.5 months (range, 3 to 53) after consolidation. Toxicity data are available in 31 grafted patients. Grade III and IV toxicities included hematologic side effects (n=31), hemorrhage (n=8), mucositis (n=24), diarrhea (n=12), renal disorders (n=8), and pneumonitis (n=3). CONCLUSION The adverse prognostic factors (APF) used to select patients for this dose-intensive chemotherapy define children with very-poor-risk recurrent WT. Despite high treatment-related toxicity, about half of these patients remain disease-free at 3 years. Patient outcome is statistically better when high-dose chemotherapy (HDCT) is performed as early as the second CR or partial response (PR). Novel therapeutic approaches with innovative preparative regimens are warranted for the remaining high-risk patients.

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Topotecan Is Active Against Wilms’ Tumor: Results of a Multi-Institutional Phase II Study

Journal of Clinical Oncology ◽

10.1200/jco.2007.10.9298 ◽

2007 ◽

Vol 25 (21) ◽

pp. 3130-3136 ◽

Cited By ~ 48

Author(s):

Monika L. Metzger ◽

Clinton F. Stewart ◽

Burgess B. Freeman ◽

Catherine A. Billups ◽

Fredric A. Hoffer ◽

...

Keyword(s):

Phase Ii ◽

Median Duration ◽

Progressive Disease ◽

Phase Ii Study ◽

Wilms Tumor ◽

Area Under The Curve ◽

Salvage Chemotherapy ◽

Target Area ◽

Favorable Histology ◽

Grade 3

Purpose A phase II study was conducted to evaluate the activity and safety of topotecan in pediatric patients with recurrent Wilms' tumor. Patients and Methods Patients with favorable histology Wilms' tumor (FHWT) and recurrence after at least one salvage chemotherapy regimen or with anaplastic histology Wilms' tumor (AHWT) in first or subsequent recurrence were eligible. Patients were stratified according to histology, with statistical considerations based on the FHWT stratum. Topotecan was administered intravenously over 30 minutes for 5 days on 2 consecutive weeks. Treatment dosages were adjusted to achieve a target area under the curve (AUC) of 80 ± 10 ng/mL*h. Tumor responses were measured after two cycles of treatment. Results Thirty-seven patients (26 patients with FHWT) were enrolled and received a total of 94 cycles of topotecan (range, one to six cycles). The median topotecan dosage required to achieve the target AUC was 1.8 mg/m2 (range, 0.7 to 3.2 mg/m2). Of 25 assessable patients with FHWT, 12 had partial response (PR), six had stable disease (SD), and seven had progressive disease (PD), for an overall response rate of 48% (95% CI, 27.8% to 68.7%). Of 11 assessable patients with AHWT, two had PR, one had SD, and eight had PD. The main toxicities were grade 3 and 4 neutropenia (median duration, 13 days) and thrombocytopenia (median duration, 7.5 days). Conclusion Topotecan administered on a protracted schedule is active against recurrent FHWT. Inclusion of topotecan in front-line clinical trials for patients with recurrent Wilms' tumor should be considered.

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