Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

PURPOSE: Preclinical data have demonstrated that farnesyltransferaseinhibitors (FTIs) are radiation sensitizers in selected cell lines. The objective of this Phase I trial was to determine the maximally tolerated dose of the FTI L-778,123 in combination with radiotherapy in non-small cell lung cancer (NSCLC) and head and neck cancer (HNC). EXPERIMENTAL DESIGN: L-778,123 was given by continuous i.v. infusion and dose escalated in conjunction with standard radiotherapy. The presence of a ras mutation was not required for study entry. RESULTS: Nine patients (six NSCLC patients and three HNC patients) were enrolled on two dose levels of FTI. No dose-limiting toxicities were observed at the first dose level of 280 mg/m2/day during weeks 1, 2, 4, and 5 of radiotherapy. One episode of dose-limiting toxicity, grade IV neutropenia, was observed in one of three patients treated at 560 mg/m2/day during weeks 1, 2, 4, 5, and 7. No episodes of dose-limiting mucositis, esophagitis, or pneumonitis were observed. Of the four patients with NSCLC with evaluable disease, three patients had a complete response to treatment and one patient had a partial response. A complete clinical response to treatment was observed in two patients with HNC. In vitro studies in tumor cells obtained from a NSCLC patient on this trial showed radiosensitization with FTI and that tumor cells accumulated in G2-M after L-778,123 treatment. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 is associated with acceptable toxicity. Local responses have been observed in four NSCLC patients without a clear increase in radiotherapy-associated toxicities.

Type

Journal article

Journal

Clin Cancer Res

Publication Date

05/2002

Volume

8

Pages

1065 - 1072

Keywords

Adult, Aged, Alkyl and Aryl Transferases, Carcinoma, Non-Small-Cell Lung, Cell Survival, Combined Modality Therapy, Dose-Response Relationship, Radiation, Farnesyltranstransferase, Female, Head and Neck Neoplasms, Hematologic Diseases, Humans, Imidazoles, Lung Neoplasms, Male, Middle Aged, Mouth Mucosa, Nausea, Skin Diseases, Stomatitis, Treatment Outcome, Tumor Cells, Cultured, Vomiting