title: VIP (etoposide, ifosfamide, cisplatin) in adult patients with recurrent or refractory Ewing sarcoma family of tumors.
abstract: Despite the fact that Ewing sarcoma family of tumors (ET) is chemosensitive, long-term survival is extremely rare for patients with primary refractory or recurrent disease. There is no standard salvage chemotherapy regimen available in this context. In this study the authors reviewed their experience with the combination of etoposide, ifosfamide, and cisplatin in adult patients with recurrent or refractory disease. From February 1997 through December 2001, they evaluated the efficacy of etoposide (75 mg/m2/day for 5 days), ifosfamide (1,200 mg/m2/day for 5 days), and cisplatin (20 mg/m2/day for 5 days) combination chemotherapy (VIP regimen), as second-line salvage therapy in 27 patients with recurrent or refractory ET. All patients were evaluated for response, time to progression, and overall survival. Twenty-one male and 6 female patients with recurrent (n = 14) and refractory (n = 13) disease were treated with the VIP regimen. Median age was 18 years (range, 16-34 years). Twenty-two patients were previously treated with vincristine, Adriamycin, ifosfamide, and actinomycin-D; and 5 patients were treated with cyclophosphamide, Adriamycin, and vincristine. Sites of recurrent or progressive disease included local (n = 3), distant (n = 11), and both local and distant (n = 13). A total of 129 cycles of VIP were given (median, 5 cycles/patient; range, 1-14 cycles/patient). One patient (4%) had a complete response (CR) and 8 patients (30%) had a partial response (PR), for an overall response rate of 34%. The median number of cycles given to patients with CR + PR was 6 (range, 3-14 cycles). Nine patients (33%) had stable disease and 9 (33%) had disease progression. Median time to progression and median overall survival were 6.6 months and 8.1 months respectively for all patients, and 12.8 months and 14.2 months respectively for responders. There were no toxic deaths. Major toxicities included grade IV granulocytopenia in 19 patients and grades III/IV thrombocytopenia in 15 patients. At a median follow-up of 8 months (range, 2-56 months), 24 patients died of disease progression, 2 patients are alive with disease, and 1 patient is alive with no evidence of disease. The authors conclude that the VIP combination is active in patients with recurrent/refractory ET, with acceptable toxicity, and offers good palliation. Cisplatin-based combination chemotherapy merits further investigation, possibly as first-line treatment in this disease.
authors.affiliation: Department of Medical Oncology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. aweshi@healthgulf.com
authors.forename: Amr
authors.initials: A
authors.lastname: El Weshi
authors.forename: Muhammad
authors.initials: M
authors.lastname: Memon
authors.forename: Madras
authors.initials: M
authors.lastname: Raja
authors.forename: Shouki
authors.initials: S
authors.lastname: Bazarbashi
authors.forename: Mohamed
authors.initials: M
authors.lastname: Rahal
authors.forename: Mahmoud
authors.initials: M
authors.lastname: El Foudeh
authors.forename: Chandrashekhar
authors.initials: C
authors.lastname: Pai
authors.forename: Ayman
authors.initials: A
authors.lastname: Allam
authors.forename: Ibrahim
authors.initials: I
authors.lastname: El Hassan
authors.forename: Adnan
authors.initials: A
authors.lastname: Ezzat
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy*; D002945:Cisplatin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use*; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D016879:Salvage Therapy; D012512:Sarcoma, Ewing / Q000188:drug therapy*; D016019:Survival Analysis
chemical_list: D005047:Etoposide; D002945:Cisplatin; D007069:Ifosfamide