Preoperative intensity-modulated radiotherapy combined with temozolomide for locally advanced soft-tissue sarcoma

Int J Radiat Oncol Biol Phys. 2009 Nov 1;75(3):810-6. doi: 10.1016/j.ijrobp.2008.11.032. Epub 2009 Mar 21.

Abstract

Purpose: To evaluate the toxicity and efficacy of preoperative intensity-modulated radiotherapy (IMRT) combined with temozolomide to improve local tumor control in soft-tissue sarcoma (STS).

Patients and methods: A cohort of 15 consecutive patients with nonmetastasized, primary high-grade or locally recurrent Stage III (n = 14) or IIb (n = 1) STS not amenable to surgical resection without significant organ or extremity function loss was prospectively investigated. Median tumor size was 9.8 cm, and most tumors were non-extremity sarcomas. Patients preoperatively received 50 mg/m(2) of temozolomide during IMRT (50.4 Gy). Resection was intended 6 weeks thereafter. Toxicity was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0, and response was assessed by Response Evaluation Criteria in Solid Tumors.

Results: Of 15 patients, 14 completed preoperative treatment. No Grade 4 toxicities occurred. Nausea and vomiting were the most frequent Grade 3 toxicities. The most frequent toxicities of any grade were dermatologic, gastrointestinal, and hematologic. Response was partial response in 5, stable disease in 7, and progressive disease in 2 patients. Ten patients underwent surgery: 7 were resected with clear margins (R0), and 2 patients had an R1 resection; in 1 patient the tumor was not resectable. Postoperative complications occurred in 4 patients. Five patients did not undergo surgery because of intercurrent metastatic disease, unresectable disease, or refusal.

Conclusions: Preoperative chemoradiation with temozolomide and IMRT can be administered safely and with promising efficacy in patients with locally advanced STS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating / adverse effects
  • Antineoplastic Agents, Alkylating / therapeutic use*
  • Combined Modality Therapy / adverse effects
  • Combined Modality Therapy / methods
  • Dacarbazine / adverse effects
  • Dacarbazine / analogs & derivatives*
  • Dacarbazine / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nausea / etiology
  • Postoperative Complications
  • Prospective Studies
  • Radiation Injuries / etiology
  • Radiotherapy Dosage
  • Radiotherapy, Intensity-Modulated* / adverse effects
  • Remission Induction
  • Sarcoma* / drug therapy
  • Sarcoma* / pathology
  • Sarcoma* / radiotherapy
  • Sarcoma* / surgery
  • Temozolomide
  • Tumor Burden
  • Vomiting / etiology

Substances

  • Antineoplastic Agents, Alkylating
  • Dacarbazine
  • Temozolomide