Abstract |
This phase I study was performed to assess the feasibility of combining cisplatin/ etoposide (VP-16) with the arotinoid Ro 40-8757 and to determine the dose-limiting toxicity (DLT) of Ro 40-8757 in this combination. Patients with non-small cell lung cancer were eligible. Treatment consisted of Ro 40-8757 p.o. day 1-21, cisplatin 100 mg/m2 i.v. on day 2 and VP-16 100 mg/m2 i.v. on day 2-4, repeated every 3 weeks. Eighteen patients were evaluable for toxicity and response. The doses of Ro 40-8757 ranged from 84 mg/m2 once daily to 42 mg/m2 thrice daily (tid). DLT consisting of delayed nausea/ vomiting was reached at 42 mg/m2 tid. Consequently, the maximum tolerated dose was set at one dose level below the DLT, i.e. 28 mg/m2 tid. Skin toxicity occurred but was well manageable. Pharmacological analyses showed a small increase in the volume of distribution of cisplatin and VP-16 between the first and third course. However, no relationship with side effects was found. A response was achieved in 50% of patients. The combination of cisplatin/ VP-16 with Ro 40-8757 appears to be feasible at a dose schedule of 28 mg/m2 tid. The response rate was at the upper rate of what can be expected with cisplatin and VP-16.
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Authors | L van Zuylen, J H Schellens, S H Goey, L C Pronk, M M de Boer-Dennert, W J Loos, J Ma, G Stoter, J Verweij |
Journal | Anti-cancer drugs
(Anticancer Drugs)
Vol. 10
Issue 4
Pg. 361-8
(Apr 1999)
ISSN: 0959-4973 [Print] England |
PMID | 10378670
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)
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Chemical References |
- Antineoplastic Agents
- Morpholines
- Retinoids
- Etoposide
- mofarotene
- Cisplatin
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Topics |
- Adult
- Aged
- Antineoplastic Agents
(administration & dosage, adverse effects)
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects)
- Carcinoma, Non-Small-Cell Lung
(drug therapy)
- Cisplatin
(administration & dosage, adverse effects, pharmacokinetics)
- Etoposide
(administration & dosage, adverse effects, pharmacokinetics)
- Female
- Humans
- Lung Neoplasms
(drug therapy)
- Male
- Metabolic Clearance Rate
- Middle Aged
- Morpholines
(administration & dosage, adverse effects, pharmacokinetics)
- Retinoids
(administration & dosage, adverse effects, pharmacokinetics)
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