Abstract | PURPOSE: 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.
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Authors | Stephen M Hahn, Eric J Bernhard, William Regine, Mohammed Mohiuddin, Daniel G Haller, James P Stevenson, Debbie Smith, Barnali Pramanik, Joel Tepper, Thomas F DeLaney, Krystina D Kiel, Briggs Morrison, Paul Deutsch, Ruth J Muschel, W Gillies McKenna |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 8
Issue 5
Pg. 1065-72
(May 2002)
ISSN: 1078-0432 [Print] United States |
PMID | 12006520
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Imidazoles
- L 778,123
- Alkyl and Aryl Transferases
- Farnesyltranstransferase
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Topics |
- Adult
- Aged
- Alkyl and Aryl Transferases
(antagonists & inhibitors)
- Carcinoma, Non-Small-Cell Lung
(drug therapy, pathology, radiotherapy)
- Cell Survival
(drug effects, radiation effects)
- Combined Modality Therapy
(adverse effects)
- Dose-Response Relationship, Radiation
- Farnesyltranstransferase
- Female
- Head and Neck Neoplasms
(drug therapy, pathology, radiotherapy)
- Hematologic Diseases
(chemically induced)
- Humans
- Imidazoles
(administration & dosage, adverse effects, therapeutic use)
- Lung Neoplasms
(drug therapy, pathology, radiotherapy)
- Male
- Middle Aged
- Mouth Mucosa
(drug effects, pathology)
- Nausea
(chemically induced)
- Skin Diseases
(chemically induced)
- Stomatitis
(chemically induced)
- Treatment Outcome
- Tumor Cells, Cultured
- Vomiting
(chemically induced)
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