Phase I study of conformal radiotherapy and concurrent full-dose gemcitabine with erlotinib for unresected pancreatic cancer

Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):e187-92. doi: 10.1016/j.ijrobp.2010.08.050. Epub 2011 May 5.

Abstract

Purpose: To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer.

Methods and materials: 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.

Results: 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.

Conclusion: The results of the present study have indicated that the recommended Phase II dose is 30 Gy in 15 fractions.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / administration & dosage*
  • Antimetabolites, Antineoplastic / adverse effects
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives*
  • Drug Administration Schedule
  • Drug Therapy, Combination / methods
  • Erlotinib Hydrochloride
  • Female
  • Gemcitabine
  • Humans
  • Infections / etiology
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Nausea / etiology
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / radiotherapy*
  • Quinazolines / administration & dosage*
  • Quinazolines / adverse effects
  • Radiation-Sensitizing Agents / administration & dosage*
  • Radiation-Sensitizing Agents / adverse effects
  • Radiotherapy Dosage
  • Radiotherapy, Conformal / adverse effects
  • Radiotherapy, Conformal / methods*
  • Time Factors
  • Tumor Burden / radiation effects
  • Vomiting / etiology

Substances

  • Antimetabolites, Antineoplastic
  • Quinazolines
  • Radiation-Sensitizing Agents
  • Deoxycytidine
  • Erlotinib Hydrochloride
  • Gemcitabine