Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities: Results of a randomized control trial in patients with advanced ovarian cancer

George Kemp, Peter Rose, John Lurain, Michael Berman, Alberto Manetta, Bernard Roullet, Howard Homesley, Dominique Belpomme, John Glick

Research output: Contribution to journalArticle

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Abstract

Purpose: Serious cumulative toxicity is a well-recognized consequence of chemotherapy. Amifostine, an organic thiophosphate, has demonstrated the ability to protect selectively a broad range of normal, but not neoplastic, tissues from the cytotoxic effects of chemotherapy and radiotherapy. This study was designed to determine if amifostine could reduce the serious toxicities associated with cyclophosphamide and cisplatin (CP), without reducing antitumor efficacy in patients with ovarian cancer. Patients and Methods: Two hundred forty-two patients with advanced ovarian cancer were randomized to receive six cycles of cyclophosphamide (1,000 mg/m2) and cisplatin (100 mg/m2) with or without amifostine (910 mg/m2) every 3 weeks for six cycles. The occurrence of hematologic, renal, neurologic, and ototoxicity was evaluated. Antitumor efficacy was assessed by pathologic tumor response and survival. Results: Pretreatment with amifostine before each cycle of chemotherapy resulted in a reduction of cumulative toxicities. Hematologic toxicity consisted of grade 4 neutropenia associated with fever and/or infection that required antibiotic therapy (P = .005), days in hospital (P = .019), and days on antibiotics (P = .031). Platinum-specific toxicities consisted of protracted serum creatinine elevations (P = 0.004), ≤ 40% reduction from baseline in creatinine clearance (P = .001), and severity of neurologic toxicity (P = .029). Twenty-four percent of CP patients compared with 9% of amifostine plus CP patients discontinued therapy because of protocol-specified toxicity (P = .002). Pathologic tumor response rates were 37% with amifostine and 28% in controls, with comparable median survival times of 31 months. Amifostine was generally well tolerated; the princiPal side effects were emesis and a transient decrease in blood pressure. Conclusion: Pretreatment with amifostine reduces the cumulative hematologic, renal, and neurologic toxicities associated with the CP regimen, with no reduction in antitumor efficacy.

LanguageEnglish (US)
Pages2101-2112
Number of pages12
JournalJournal of Clinical Oncology
Volume14
Issue number7
DOIs
StatePublished - Jan 1 1996

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Amifostine
Ovarian Neoplasms
Cyclophosphamide
Cisplatin
Nervous System
Drug Therapy
Creatinine
Anti-Bacterial Agents
Kidney
Survival
Neutropenia
Platinum
Vomiting
Neoplasms
Reference Values
Fever
Radiotherapy
Blood Pressure

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kemp, George ; Rose, Peter ; Lurain, John ; Berman, Michael ; Manetta, Alberto ; Roullet, Bernard ; Homesley, Howard ; Belpomme, Dominique ; Glick, John. / Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities : Results of a randomized control trial in patients with advanced ovarian cancer. In: Journal of Clinical Oncology. 1996 ; Vol. 14, No. 7. pp. 2101-2112
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Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities : Results of a randomized control trial in patients with advanced ovarian cancer. / Kemp, George; Rose, Peter; Lurain, John; Berman, Michael; Manetta, Alberto; Roullet, Bernard; Homesley, Howard; Belpomme, Dominique; Glick, John.

In: Journal of Clinical Oncology, Vol. 14, No. 7, 01.01.1996, p. 2101-2112.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities

T2 - Journal of Clinical Oncology

AU - Kemp,George

AU - Rose,Peter

AU - Lurain,John

AU - Berman,Michael

AU - Manetta,Alberto

AU - Roullet,Bernard

AU - Homesley,Howard

AU - Belpomme,Dominique

AU - Glick,John

PY - 1996/1/1

Y1 - 1996/1/1

N2 - Purpose: Serious cumulative toxicity is a well-recognized consequence of chemotherapy. Amifostine, an organic thiophosphate, has demonstrated the ability to protect selectively a broad range of normal, but not neoplastic, tissues from the cytotoxic effects of chemotherapy and radiotherapy. This study was designed to determine if amifostine could reduce the serious toxicities associated with cyclophosphamide and cisplatin (CP), without reducing antitumor efficacy in patients with ovarian cancer. Patients and Methods: Two hundred forty-two patients with advanced ovarian cancer were randomized to receive six cycles of cyclophosphamide (1,000 mg/m2) and cisplatin (100 mg/m2) with or without amifostine (910 mg/m2) every 3 weeks for six cycles. The occurrence of hematologic, renal, neurologic, and ototoxicity was evaluated. Antitumor efficacy was assessed by pathologic tumor response and survival. Results: Pretreatment with amifostine before each cycle of chemotherapy resulted in a reduction of cumulative toxicities. Hematologic toxicity consisted of grade 4 neutropenia associated with fever and/or infection that required antibiotic therapy (P = .005), days in hospital (P = .019), and days on antibiotics (P = .031). Platinum-specific toxicities consisted of protracted serum creatinine elevations (P = 0.004), ≤ 40% reduction from baseline in creatinine clearance (P = .001), and severity of neurologic toxicity (P = .029). Twenty-four percent of CP patients compared with 9% of amifostine plus CP patients discontinued therapy because of protocol-specified toxicity (P = .002). Pathologic tumor response rates were 37% with amifostine and 28% in controls, with comparable median survival times of 31 months. Amifostine was generally well tolerated; the princiPal side effects were emesis and a transient decrease in blood pressure. Conclusion: Pretreatment with amifostine reduces the cumulative hematologic, renal, and neurologic toxicities associated with the CP regimen, with no reduction in antitumor efficacy.

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