Phase I study of irinotecan and raltitrexed in patients with advanced gastrointestinal tract adenocarcinoma.
Br J Cancer
; 83(2): 146-52, 2000 Jul.
Article
en En
| MEDLINE
| ID: mdl-10901362
ABSTRACT
To determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of irinotecan and raltitrexed given as sequential short infusions every 3 weeks, 33 patients with pretreated gastrointestinal adenocarcinoma (31 colorectal, 2 oesophagogastric) entered this open label dose-escalation study. For the first five dose levels patients received irinotecan 175-350 mg m(-2) followed by raltitrexed 2.6 mg m(-2). Level VI was irinotecan 350 mg m(-2) plus raltitrexed 3.0 mg m(-2), level VII was irinotecan 400 mg m(-2) plus raltitrexed 2.6 mg m(-2); 261 courses were administered. Only one patient at dose levels I-V experienced DLT. At level VI, 5/12 patients experienced DLT one had grade 3 diarrhoea and lethargy, one had grade 4 diarrhoea and one had lethargy alone. Two others had lethargy caused by disease progression. There was no first-cycle neutropenia. At level VII, 3/6 patients experienced dose-limiting lethargy, one also had grade 3 diarrhoea. Dose intensity fell from over 90% for both drugs at level VI to 83% for irinotecan and 66% for raltitrexed at level VII. Lethargy was therefore the DLT, and level VII the MTD. Pharmacokinetic data showed no measurable drug interaction; 6/30 patients (20%) had objective responses. This combination is active with manageable toxicity. Recommended doses for further evaluation are irinotecan 350 mg m(-2) and raltitrexed 3.0 mg m(-2).
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Camptotecina
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Adenocarcinoma
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Protocolos de Quimioterapia Combinada Antineoplásica
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Neoplasias Gastrointestinales
Límite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Br J Cancer
Año:
2000
Tipo del documento:
Article
País de afiliación:
Reino Unido