Improved Local Control with RSR-13 and Concurrent Radiation Therapy in a Phase II Study for Locally Advanced Inoperable Non-Small Cell Lung Cancer

William Levin, MD
University of Pennsylvania Cancer Center
Last Modified: November 7, 2001

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Presenter: H. Choy
Presenter's Affiliation: Vanderbilt University Medical Center, Nashville, TN
Type of Session: Scientific

Background
RSR13 is a synthetic allosteric modifier of hemeglobin (Hb). It decreases Hb-oxygen binding affinity by causing a change in the shape of the Hb tetramer molecule. This change results in an increase in tumor oxygenation by enhancing diffusion of oxygen from blood into the tissues. Radiation therapy would theoretically be more effective in killing tumor cells if oxygenation was increased.

Materials and Methods

  • This is a Phase II open-label study of a daily infusion of RSR13 and thoracic radiation therapy (TRT) following induction chemotherapy for non-small cell lung cancer (NSCLCA).
  • 50 patients were enrolled.
  • Patients had Stage IIIa or IIIb NSCLCA.
  • KPS was > or =70.
  • < or =10% weight loss in the 3 months prior to enrollment.
  • Induction chemotherapy: paclitaxel (225 mg/m2)IV and carboplatin (AUC=6) x2 cycles.
  • TRT: 64 Gy in 32 fractions within 4 weeks of chemotherapy.
  • RSR13: 50-100 mg/kg IV, daily prior to TRT.

    Results

  • Over 80% of patients received at least 80% of the planned chemotherapy.
  • 75% of patients received more than 90% of the planned dose of RSR13.
  • Of the 44 evauluable patients, 88% had either a partial or complete response (79% PR).
  • On Kaplan-Meyer analysis, with a median follow-up of 20 months, median survival and progression free survival was 20.6 and 9.9 months, respectively.
  • Estimated 1 and 2 year overall survival was 68 and 43%, respectively.
  • Grade 3/4 toxicity from chemotherapy: 12% granulocytopenia; 4% vomiting; 4% fatigue.
  • Grade 3/4 toxicity from RSR13 and TRT: 19% hypoxia; 13% RT pneumonitis; 9% dyspnea.

    Author's Conclusions

  • RSR13 was well tolerated.
  • Induction paclitaxel/carboplatin chemotherapy followed by concurrent infusion of RSR13 and TRT offers significant clinical benefit in the management of Stage III NSCLCA.

    Clinical/Scientific Implications

  • The idea of increasing tumor oxygenation by decreasing hemeglobin-oxygen binding affinity is not a new idea, but one that has yet to be fully developed. RSR13 is an exciting and novel compound that may offer promise in the realization of this goal, but further testing is needed.

    Oncolink's ASTRO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology and Pharmacia Oncology.



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