Carboplatin combined with amifostine, a bone marrow protectant, in the treatment of non-small-cell lung cancer: a randomised phase II study.

2.50
Hdl Handle:
http://hdl.handle.net/10541/99262
Title:
Carboplatin combined with amifostine, a bone marrow protectant, in the treatment of non-small-cell lung cancer: a randomised phase II study.
Authors:
Betticher, Daniel C; Anderson, Heather; Ranson, Malcolm R; Meely, K; Oster, W; Thatcher, Nick
Abstract:
Amifostine (WR-2721), a thiol compound, has been shown to protect normal tissue from alkylating agents and cisplatin-induced toxicity without loss of anti-tumour effects. To confirm this result, we conducted a phase II randomised trial to determine if the addition of amifostine reduces the toxicity of carboplatin without loss of anti-tumour activity in patients with inoperable non-small-cell lung cancer (NSCLC). After the first course of carboplatin (600 mg m-2 i.v. infusion), 21 patients were randomised to receive three cycles of carboplatin alone (C arm) or three infusions of amifostine at 910 mg m-2 (CA arm) at 28 day intervals. The amifostine was given 20 min before and at 2 and 4 h after carboplatin. Since the 910 mg m-2 amifostine infusion led to hypotension in six patients, the dosage was reduced by 25%, to 683 mg m-2 t.i.d., in the other four patients. Amifostine was well tolerated at this dose level. Five patients in the CA arm and three in the C arm had their planned treatment discontinued owing to progressive disease (n = 3), amifostine side-effects (hypotension, sneezing and sickness, n = 4), and carboplatin-induced thrombocytopenia (n = 1). Bone marrow and renal function at study entry and after the first course of carboplatin before randomisation were similar in both treatment arms. Twenty courses of carboplatin+amifostine have been compared with 25 courses of carboplatin alone. Although there was no statistically significant difference with respect to haematological values comparing both arms, the median time to platelet recovery (> 100 x 10(9) l-1) (13.5 days vs 21 days; P = 0.04) and the need for hospitalisation for i.v. antibiotic and other supportive treatment tended to be reduced in the CA arm (0/20 vs 6/25 patient courses; P = 0.06). Response rates and median survival (14 vs 9 months) were no different, excluding tumour protection activity by amifostine. These results with a small number of patients suggest that amifostine given with carboplatin may reduce the duration of thrombocytopenia and hospitalisation.
Affiliation:
CRC Department of Medical Oncology, Christie and Wythenshawe Hospitals, Manchester, UK.
Citation:
Carboplatin combined with amifostine, a bone marrow protectant, in the treatment of non-small-cell lung cancer: a randomised phase II study. 1995, 72 (6):1551-5 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
Dec-1995
URI:
http://hdl.handle.net/10541/99262
PubMed ID:
8519676
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorBetticher, Daniel Cen
dc.contributor.authorAnderson, Heatheren
dc.contributor.authorRanson, Malcolm Ren
dc.contributor.authorMeely, Ken
dc.contributor.authorOster, Wen
dc.contributor.authorThatcher, Nicken
dc.date.accessioned2010-05-19T10:01:58Z-
dc.date.available2010-05-19T10:01:58Z-
dc.date.issued1995-12-
dc.identifier.citationCarboplatin combined with amifostine, a bone marrow protectant, in the treatment of non-small-cell lung cancer: a randomised phase II study. 1995, 72 (6):1551-5 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid8519676-
dc.identifier.urihttp://hdl.handle.net/10541/99262-
dc.description.abstractAmifostine (WR-2721), a thiol compound, has been shown to protect normal tissue from alkylating agents and cisplatin-induced toxicity without loss of anti-tumour effects. To confirm this result, we conducted a phase II randomised trial to determine if the addition of amifostine reduces the toxicity of carboplatin without loss of anti-tumour activity in patients with inoperable non-small-cell lung cancer (NSCLC). After the first course of carboplatin (600 mg m-2 i.v. infusion), 21 patients were randomised to receive three cycles of carboplatin alone (C arm) or three infusions of amifostine at 910 mg m-2 (CA arm) at 28 day intervals. The amifostine was given 20 min before and at 2 and 4 h after carboplatin. Since the 910 mg m-2 amifostine infusion led to hypotension in six patients, the dosage was reduced by 25%, to 683 mg m-2 t.i.d., in the other four patients. Amifostine was well tolerated at this dose level. Five patients in the CA arm and three in the C arm had their planned treatment discontinued owing to progressive disease (n = 3), amifostine side-effects (hypotension, sneezing and sickness, n = 4), and carboplatin-induced thrombocytopenia (n = 1). Bone marrow and renal function at study entry and after the first course of carboplatin before randomisation were similar in both treatment arms. Twenty courses of carboplatin+amifostine have been compared with 25 courses of carboplatin alone. Although there was no statistically significant difference with respect to haematological values comparing both arms, the median time to platelet recovery (> 100 x 10(9) l-1) (13.5 days vs 21 days; P = 0.04) and the need for hospitalisation for i.v. antibiotic and other supportive treatment tended to be reduced in the CA arm (0/20 vs 6/25 patient courses; P = 0.06). Response rates and median survival (14 vs 9 months) were no different, excluding tumour protection activity by amifostine. These results with a small number of patients suggest that amifostine given with carboplatin may reduce the duration of thrombocytopenia and hospitalisation.en
dc.language.isoenen
dc.subjectLung Canceren
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAmifostine-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshBone Marrow Diseases-
dc.subject.meshCarboplatin-
dc.subject.meshCarcinoma, Non-Small-Cell Lung-
dc.subject.meshDrug Administration Schedule-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshLung Neoplasms-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshRadiation-Protective Agents-
dc.titleCarboplatin combined with amifostine, a bone marrow protectant, in the treatment of non-small-cell lung cancer: a randomised phase II study.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Medical Oncology, Christie and Wythenshawe Hospitals, Manchester, UK.en
dc.identifier.journalBritish Journal of Canceren

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