Phase I Study of Conformal Radiotherapy and Concurrent Full-Dose Gemcitabine With Erlotinib for Unresected Pancreatic Cancer
To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer.
Patients with unresected pancreatic cancer (Zubrod performance status 0-2) were eligible for the present study. Gemcitabine was given weekly for 7 weeks (1,000 mg/m(2)) with erlotinib daily for 8 weeks (100 mg). A final toxicity assessment was performed in Week 9. Radiotherapy (starting at 30 Gy in 2-Gy fractions, 5 d/wk) was given to the gross tumor plus a 1-cm margin starting with the first dose of gemcitabine. A standard 3 plus 3 dose escalation (an additional 4 Gy within 2 days for each dose level) was used, except for the starting dose level, which was scheduled to contain 6 patients. In general, Grade 3 or greater gastrointestinal toxicity was considered a dose-limiting toxicity, except for Grade 3 anorexia or Grade 3 fatigue alone.
A total of 20 patients were treated (10 men and 10 women). Nausea, vomiting, and infection were significantly associated with the radiation dose (p = .01, p = .03, and p = .03, respectively). Of the 20 patients, 5 did not complete treatment and were not evaluable for dose-escalation purposes (3 who developed progressive disease during treatment and 2 who electively discontinued it). Dose-limiting toxicity occurred in none of 6 patients at 30 Gy, 2 of 6 at 34 Gy, and 1 of 3 patients at 38 Gy.
The results of the present study have indicated that the recommended Phase II dose is 30 Gy in 15 fractions.
Available from: Emma Searle
- "Survival encouraging of further investigation. Erlotinib  2011 I Pancreatic carcinoma 30 Gy þ gemcitabine þ erlotinib Study supports phase II evaluation Erlotinib  "
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ABSTRACT: Recent drug discovery developments in the field of small molecule targeted agents have led to much interest in combining these with radiotherapy. There are good preclinical data to suggest this approach worthy of investigation and in this review we discuss how this has translated into recent clinical trials. The outcome of clinical trials investigating radiotherapy/targeted drug combinations published in the last 5 years is discussed, as are trials in progress. The perceived future opportunities and challenges in the development of this exciting area are considered.
Clinical Oncology 03/2014; 26(5). DOI:10.1016/j.clon.2014.02.006 · 3.40 Impact Factor
Available from: Anne Hansen Ree
- "Gy once daily/25 days Preoperative Safety and efficacy Toxicity and response determined Safe and active combination II 2010  Esophageal AC ERBB2 Paclitaxel and cisplatin 1.8 Gy once daily/28 days Local disease control Safety Toxicity determined No additional toxicity I 2004  Esophageal AC ERBB2 Paclitaxel and cisplatin 1.8 Gy once daily/28 days Local disease control Efficacy Response determined No additional response I/II 2007  Esophageal AC or SCC EGFR Tegafur and oxaliplatin 1.8 Gy once daily/33 days Local disease control Safety, tolerability, and efficacy DLT, MTD, and response determined Safe combination with significant response I 2012  Esophageal AC or SCC EGFR Irinotecan and cisplatin 1.8 Gy once daily/28 days Local disease control Safety and efficacy Toxicity and response determined, trial terminated Significant toxicity II 2012  Esophageal AC EGFR and VEGF (two agents) 5-FU, paclitaxel, and carboplatin 1.8 Gy once daily/25 days Preoperative Safety and efficacy Toxicity and response determined No additional response II 2012  6 Targeted drugs and radiotherapy Abdomen Pancreatic AC EGFR Gemcitabine 1.8 Gy once daily/28 days Local disease control Safety Toxicity determined Acceptable toxicity I 2011  Pancreatic AC EGFR Gemcitabine 1.8 Gy once daily/28 days Local disease control Safety, tolerability, and efficacy DLT, MTD, and response determined Active and reasonably well tolerated combination I 2008  Pancreatic AC EGFR Gemcitabine 2.0. Gy once daily/15– 19 days Local disease control Safety and tolerability DLT and MTD determined Phase 2 radiation dose determined I 2012  Pancreatic AC EGFR Capecitabine 1.8 Gy once daily/28 days Preoperative Safety DLT in 6 of 10 patients, trial terminated Significant toxicity I 2006  Pancreatic AC EGFR Paclitaxel 1.8 Gy once daily/28 days Local disease control Safety and tolerability Toxicity determined Acceptable toxicity I 2009  "
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ABSTRACT: New strategies to facilitate the improvement of physical and integrated biological optimization of high-precision treatment protocols are an important priority for modern radiation oncology. From a clinical perspective, as knowledge accumulates from molecular radiobiology, there is a complex and exciting opportunity to investigate novel approaches to rational patient treatment stratification based on actionable tumor targets, together with the appropriate design of next-generation early-phase radiotherapy trials utilizing targeted therapeutics, to formally evaluate relevant clinical and biomarker endpoints. A unique aspect in the development pathway of systemic agents with presumed radiosensitizing activity will also be the need for special attention on patient eligibility and the rigorous definition of radiation dose-volume relationships and potential dose-limiting toxicities. Based on recent experience from systematically investigating histone deacetylase inhibitors as radiosensitizing agents, from initial studies in preclinical tumor models through the conduct of a phase I clinical study to evaluate tumor activity of the targeted agent as well as patient safety and tumor response to the combined treatment modality, this communication will summarize principles relating to early clinical evaluation of combining radiotherapy and targeted therapeutics.
Radiotherapy and Oncology 07/2013; 108(1). DOI:10.1016/j.radonc.2013.06.007 · 4.36 Impact Factor
Available from: pancreascare.com
- "The relatively small sample size of the concurrent erlotinib subset as well as the lower RT dose used (mostly less than 36 Gy) prohibited meaningful statistical comparison. Continued investigation will be needed to understand the optimal approach to incorporate erlotinib with GemRT . This study highlights a need of systematic and well-designed randomized trials to clarify the optimal treatment approach for LAPC. "
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ABSTRACT: To retrospectively compare the efficacy and toxicity of full-dose gemcitabine based chemoradiotherapy (GemRT) versus 5-fluorouracil (5-FU) based chemoradiotherapy (5FURT) for locally advanced pancreas cancer (LAPC).
From January 1998 to December 2008, 93 patients with LAPC were treated either with 5FURT (n=38) or GemRT (n=55). 5FURT consisted of standard-field radiotherapy given concurrently with infusional 5-FU or capecitabine. GemRT consisted of involved-field radiotherapy given concurrently with full-dose gemcitabine (1000mg/m(2) weekly) with or without erlotinib. The follow-up time was calculated from the time of diagnosis to the date of death or last contact.
Patient characteristics were not significantly different between treatment groups. The overall survival (OS) was significantly better for GemRT compared to 5FURT (median 12.5months versus 10.2months; 51% versus 34% at 1year; 12% versus 0% at 3years; 7% versus 0% at 5years, respectively; all P=0.04). The OS benefit of GemRT was maintained on subset analysis without concurrent erlotinib or with sequential gemcitabine (all P<0.05). The rates of distant metastasis, subsequent hospitalization, acute and late grade 3-5 gastrointestinal toxicities were not significantly different between the GemRT and 5FURT groups.
GemRT was associated with an improved OS compared to standard 5FURT. This approach yielded long-term survivors and was not associated with increased hospitalization or severe gastrointestinal toxicity.
Radiotherapy and Oncology 05/2011; 99(2):114-9. DOI:10.1016/j.radonc.2011.05.038 · 4.36 Impact Factor
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