NEW HAVEN, Connecticut‘‘We’ve hit the wall in management of
small- cell lung cancer (SCLC). We need a paradigm shift," John R. Murren,
MD, stated. He is associate professor of medicine at Yale University School of
Medicine in New Haven, Connecticut.
"Escalated-dose trials have shown that intensification to the maximum
tolerated dose (MTD) of cyclophosphamide (Cytoxan, Neosar), doxorubicin (Adriamycin),
and vincristine (Oncovin) (CAV) or etoposide (VePesid) and cisplatin (Platinol)(EP)
increases toxicity without impact on survival. Dose intensification by interval
compression improves survival, but chemotherapy must be given without excessive
toxicity, and both the regimen and patient factors define the risk of
toxicity," he continued.
Risk Factors of Early Death with Chemotherapy
Dr. Murren reviewed four studies of risk factors associated with early death
with chemotherapy. These were conducted by the Manchester Lung Study Group, the
London Lung Study Group, the Medical Research Council (MRC) Lung Cancer Working
Party, and the Copenhagen Lung Cancer Group.
The MRC study of deaths in the first 3 weeks of chemotherapy found that risk
of death was greatest for patients with performance status (PS) of 2 or
greater, white blood cell count of 10,000/µL or higher, or undergoing treatment
with four or more drugs. "There was 16.7% excess mortality in the
high-risk group during the second week of treatment, and 3-year survival in
this group was only 0.6%," Dr. Murren said.
The Copenhagen Lung Cancer Group study found that early death was associated
with age of 65 or older, performance status of 3 or 4, or lactate dehydrogenase
(LDH) levels higher than two times normal. "In the high risk group, median
survival time was 133 days, and 2-year survival was 4%. Mortality during the
first chemotherapy cycle was 33% and was as high as 41% with certain
chemotherapy combinations," Dr. Murren explained. "More than half of
early deaths occurred in elderly patients with high LDH and good performance