A phase I study of erlotinib in combination with gemcitabine and radiation in locally advanced, non-operable pancreatic adenocarcinoma Journal Article
| Authors: | Duffy, A.; Kortmansky, J.; Schwartz, G. K.; Capanu, M.; Puleio, S.; Minsky, B.; Saltz, L.; Kelsen, D. P.; O'Reilly, E. M. |
| Article Title: | A phase I study of erlotinib in combination with gemcitabine and radiation in locally advanced, non-operable pancreatic adenocarcinoma |
| Abstract: | Purpose: To determine the maximum tolerated dose (MTD) of erlotinib when administered concurrently with twice weekly gemcitabine and radiation therapy (RT) for locally advanced pancreatic cancer, assess the safety and toxicity profile of this combination and secondarily evaluate response, time to tumor progression and overall survival. Methods: Patients with untreated locally advanced pancreas cancer were treated with daily erlotinib in combination with gemcitabine 40 mg/m2/30 min twice weekly and RT delivered at 180 cGy/day in 28 fractions over 5.5 weeks for a total of 5040 cGy. Erlotinib was dose escalated in successive cohorts (100 mg, 125 mg). When the MTD was determined, the cohort was expanded to better define toxicity and preliminarily efficacy. All patients were surgically staged. After chemoradiation, patients received maintenance weekly gemcitabine 1000 mg/m2 on days 1 and 8 of a 21 day cycle and daily erlotinib for four cycles. Results: Three patients were treated at dose level 1 (erlotinib 100 mg) without limiting toxicity. Two of six patients at dose level 2 (erlotinib 125 mg) had dose-limiting toxicities, neutropenia and thrombocytopenia, causing dose delay and elevated liver enzymes. The MTD for erlotinib in combination with twice weekly gemcitabine-based chemoradiation was 100 mg/day. Eleven additional patients were treated at dose level 1. All twenty patients were assessable for toxicity. Seventeen patients were assessable for response. The partial response rate was 35% and 53% had stable disease. The median survival for all patients was 18.7 months. Conclusion: In combination with fixed dose gemcitabine at 40 mg/m2 twice weekly and radiation at 180 cGy/day, the MTD of erlotinib was found to be 100 mg/day. This is a relatively well tolerated, biologically active combination in a poor prognostic cancer. © 2007 European Society for Medical Oncology. |
| Keywords: | adult; cancer survival; clinical article; treatment outcome; aged; middle aged; survival analysis; overall survival; clinical trial; disease course; fatigue; neutropenia; erlotinib; advanced cancer; cancer combination chemotherapy; diarrhea; dose response; drug dose reduction; drug efficacy; drug safety; gastrointestinal hemorrhage; gemcitabine; cancer radiotherapy; pancreas cancer; combined modality therapy; pancreatic neoplasms; radiotherapy, adjuvant; adenocarcinoma; multiple cycle treatment; anemia; antimetabolites, antineoplastic; thrombocytopenia; antineoplastic combined chemotherapy protocols; continuous infusion; lymphocytopenia; rash; protein kinase inhibitors; disease progression; pancreas adenocarcinoma; inoperable cancer; maximum tolerated dose; phase 1 clinical trial; deoxycytidine; quinazolines; chemoradiation; phase i; esophagogastroduodenoscopy |
| Journal Title: | Annals of Oncology |
| Volume: | 19 |
| Issue: | 1 |
| ISSN: | 0923-7534 |
| Publisher: | Oxford University Press |
| Date Published: | 2008-01-01 |
| Start Page: | 86 |
| End Page: | 91 |
| Language: | English |
| DOI: | 10.1093/annonc/mdm441 |
| PUBMED: | 17878176 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 37" - "Export Date: 17 November 2011" - "CODEN: ANONE" - "Source: Scopus" |
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