SAN FRANCISCOUsed with concurrent radiation therapy after
induction chemotherapy, an investigational agent that decreases hemoglobin’s
oxygen-binding affinity produced good response rates and favorable projected
survival rates in patients with unresectable non-small-cell lung cancer
Decreased affinity for hemoglobin caused by the agent, RSR13,
increases tissue oxygenation, allowing radiation to produce more free radicals,
therefore killing more tumor cells, said Hak Choy, MD, Vanderbilt University
Medical Center. In hypoxic tumors without free radicals, radiation-damaged DNA
can be repaired, allowing tumor cells to survive, Dr. Choy said in an interview
at the 37th Annual Meeting of the American Society of Clinical Oncology (ASCO).
Dr. Choy and his colleagues conducted a prospective,
open-label, multicenter phase II study with endpoints of response rate,
toxicity, and survival. The study included 52 patients with locally advanced,
unresectable stage IIIA and IIIB NSCLC from 13 institutions.
Patients received two cycles of induction paclitaxel (Taxol)
(225 mg/m2) and carboplatin (AUC 6), followed by a daily infusion of
RSR13 (75 mg/kg, with possible adjustments to 100 or 50 mg/kg) over 30 minutes
prior to thoracic radiation therapy (32 fractions at 2 Gy for a total of 64 Gy
over 7 weeks). Dr. Choy said that 71% of patients completed more than 90% of
After 2 months of follow-up, with 44 patients evaluable, the
overall response rate was 88.6% (see Table). With median follow-up of 11.5
months, estimated overall survival at 1 year was 64.7%, and projected 2-year
survival was 50.8%. Median survival time has not been reached, but was
estimated at 14 months.
Dr. Choy commented: "If you give paclitaxel and
carboplatin followed by radiation alone, you would expect a response rate in
the 55% to 65% range, with an estimated 1-year survival in the 55% to 65% range
and a 2-year survival in the 30% to 35% range, or at best 40%."
Dr. Choy said that extreme caution was exercised because of
potential problems with hypoxemia in such advanced lung cancer patients.
Patients were given face masks and a full liter of oxygen during the infusion.
He noted, however, that difficulties were less than anticipated, and that with
the drug’s short (15 minute) half-life, hypoxemia occurred in only 19% of
patients and was transient.
Grade 3-4 treatment-related radiation pneumonitis was seen in
13% of patients and grade 3-4 dyspnea in 9%. Most patients could go home within
15 to 30 minutes of treatment. "Importantly, this is not a cytotoxic drug,
so there were no other side effects," Dr. Choy added.
More study is needed, Dr. Choy said, noting also that the
regimen is somewhat difficult to deliver because of the need to monitor
Session discussant Mitchell Machtay, MD, Hospital of the
University of Pennsylvania, mentioned that hypoxia is associated with radiation
therapy resistance, angiogenesis, and poor radiation therapy outcome in many
types of solid tumorsand is extremely common in NSCLC. He found the RSR13
response rates and projected survival to be favorable.
"Toxicity was acceptable, and it is important to note that
there was no esophagitis," Dr. Machtay said. "The 89% response rate
is quite good and is comparable to, if not better than, many concurrent
chemoradiation series." He cautioned that the follow-up period was short,
and it remains to be seen whether response rates will hold up on longer