Abstract | PURPOSE: METHODS AND MATERIALS: The protocol consisted of oral gefitinib 250 mg daily for 1 year plus intravenous oxaliplatin 85 or 100 mg/m(2) on days 1, 15, and 29, and RT (50.4 Gy in 28 1.8-Gy fractions). Four-quadrant biopsies were obtained at 1-cm intervals along the length of the tumor before and after treatment and the specimens were immunostained for EGFR, Erk, Akt, and their phosphorylated (activated) forms. RESULTS: Enrollment was halted at 6 evaluable cases [all male; median age, 72.5 years (range, 51-75); and all with Eastern Cooperative Oncology Group performance status of 1]. All 6 tumors were adenocarcinomas; 5 were stage III and 1 stage IVA. Oxaliplatin was given at 85 mg/m(2) in 3 cases and at 100 mg/m(2) in 3 cases. Gefitinib therapy lasted a median 24 weeks; the median number of oxaliplatin doses was 6.5. Best responses were mucosal complete response (n = 1), partial response (n = 1), stable disease (n = 1), and progressive disease (n = 3). EGFR was expressed by tumor in 5 cases and Erk and Akt in 6 cases before treatment; no changes were noted after treatment. EGFR expression did not correlate with survival or response. No grade 4 toxicities were noted; grade 3 toxicities were diarrhea (n = 1), vomiting (n = 1), fatigue (n = 1), and constipation (n = 2). Median overall and disease-free survival times were 10.8 months and 8.4 months. CONCLUSIONS:
Gefitinib in combination with oxaliplatin and RT was tolerable, but had limited clinical activity and did not down-regulate total or activated EGFR, Akt, or Erk in esophageal tumor samples.
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Authors | Milind Javle, Amitkumar Pande, Renuka Iyer, Gary Yang, Charles LeVea, Gregory Wilding, Jennifer Black, Hector Nava, Chukwumere Nwogu |
Journal | American journal of clinical oncology
(Am J Clin Oncol)
Vol. 31
Issue 4
Pg. 329-34
(Aug 2008)
ISSN: 1537-453X [Electronic] United States |
PMID | 18845990
(Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Organoplatinum Compounds
- Quinazolines
- Oxaliplatin
- ErbB Receptors
- Proto-Oncogene Proteins c-akt
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
- Gefitinib
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Topics |
- Adenocarcinoma
(drug therapy, radiotherapy, secondary, therapy)
- Aged
- Antineoplastic Combined Chemotherapy Protocols
(therapeutic use)
- Carcinoma, Squamous Cell
(drug therapy, radiotherapy, secondary, therapy)
- Combined Modality Therapy
- ErbB Receptors
(metabolism)
- Esophageal Neoplasms
(drug therapy, pathology, radiotherapy, therapy)
- Female
- Gefitinib
- Humans
- Immunoenzyme Techniques
- Male
- Maximum Tolerated Dose
- Middle Aged
- Mitogen-Activated Protein Kinase 1
(metabolism)
- Mitogen-Activated Protein Kinase 3
(metabolism)
- Organoplatinum Compounds
(administration & dosage)
- Oxaliplatin
- Phosphorylation
- Pilot Projects
- Prognosis
- Proto-Oncogene Proteins c-akt
(metabolism)
- Quinazolines
(administration & dosage)
- Survival Rate
- Treatment Outcome
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