Radiation therapy with full-dose gemcitabine and oxaliplatin for unresectable pancreatic cancer

Int J Radiat Oncol Biol Phys. 2012 Jul 1;83(3):921-6. doi: 10.1016/j.ijrobp.2011.08.022. Epub 2011 Dec 28.

Abstract

Purpose: We completed a Phase I trial of gemcitabine and oxaliplatin with concurrent radiotherapy in patients with previously untreated pancreatic cancer. The results of a subset of patients with unresectable disease who went on to receive planned additional therapy are reported here.

Methods and materials: All patients received two 28-day cycles of gemcitabine (1,000 mg/m(2) on Days 1, 8, and 15) and oxaliplatin (40-85 mg/m(2) on Days 1 and 15, per a dose-escalation schema). Radiation therapy was delivered concurrently with Cycle 1 (27 Gy in 1.8-Gy fractions). At 9 weeks, patients were reassessed for resectability. Those deemed to have unresectable disease were offered a second round of treatment consisting of 2 cycles of gemcitabine and oxaliplatin and 27 Gy of radiation therapy (total, 54 Gy). Radiation was delivered to the gross tumor volume plus 1 cm by use of a three-dimensional conformal technique. We used the Common Terminology Criteria for Adverse Events to assess acute toxicity. Late toxicity was scored per the Radiation Therapy Oncology Group scale. Computed tomography scans were reviewed to determine pattern of failure, local response, and disease progression. Kaplan-Meier methodology and Cox regression models were used to evaluate survival and freedom from failure.

Results: Thirty-two patients from the Phase I dose-escalation study had unresectable disease, three of whom had low-volume metastatic disease. Of this group, 16 patients went on to receive additional therapy to complete a total of 4 cycles of chemotherapy and 54 Gy of concurrent radiation. For this subset, 38% had at least a partial tumor response at a median of 3.2 months. Median survival was 11.8 months (range, 4.4-26.3 months). The 1-year freedom from local progression rate was 93.8% (95% confidence interval, 63.2-99.1).

Conclusions: Radiation therapy to 54 Gy with concurrent full-dose gemcitabine and oxaliplatin is well tolerated and results in favorable rates of local tumor response and 1-year freedom from local progression.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Chemoradiotherapy / adverse effects
  • Chemoradiotherapy / methods*
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Drug Administration Schedule
  • Feasibility Studies
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Pancreatic Neoplasms / mortality
  • Pancreatic Neoplasms / pathology
  • Pancreatic Neoplasms / therapy*
  • Radiation-Sensitizing Agents / therapeutic use*
  • Radiotherapy Dosage
  • Radiotherapy, Conformal / adverse effects
  • Radiotherapy, Conformal / methods*
  • Retreatment / methods
  • Tumor Burden

Substances

  • Organoplatinum Compounds
  • Radiation-Sensitizing Agents
  • Oxaliplatin
  • Deoxycytidine
  • Gemcitabine