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Topotecan Used in Aggressive Front-Line Therapy for SCLC

Topotecan Used in Aggressive Front-Line Therapy for SCLC

NEW YORK—A study of an aggressive front-line regimen for
limited-stage small-cell lung cancer (SCLC) is proceeding in a community-based
setting. The regimen consists of topotecan (Hycamtin), carboplatin
(Paraplatin), and paclitaxel (Taxol) along with radiation therapy. Howard A.
Burris III, MD, director of drug development, The Sarah Cannon Cancer Center,
Nashville, described the study rationale and design at the Chemotherapy
Foundation Symposium XIX (abstract 62).

The trial is being conducted via the Minnie Pearl Research Network, a
consortium of community-based physicians throughout the Southeast. In 14
months, 78 of the projected 100 patients have been enrolled. "It’s
clear," Dr. Burris said, "that the doctors are interested in pursuing
this sort of aggressive therapy."

The rationale for the drug triplet, Dr. Burris said, stems from preclinical
studies showing evidence of topotecan’s synergism with both taxanes and
platinums. An inhibitor of topoisomerase I, topotecan has a half-life of 3 to
4 hours, "which is nice for combining with other drugs," he said. Its
renal excretion differs from the hepatic metabolism of most cancer drugs, he
added.

The protocol calls for paclitaxel at 135 mg/m², carboplatin to AUC 5, and
topotecan at 0.75 mg/m². The topotecan dose, Dr. Burris noted, is half that
generally used in other settings and is administered only on the first 3 days
of the 21-day cycles. Thoracic radiation at 61.2 Gy is given concurrently with
the chemotherapy in cycles 3 and 4. After completion of therapy, responders
receive oral etoposide (VePesid).

Previous Phase II Study

The chemotherapy regimen is the same as that used in a prior phase II study
completed by the Minnie Pearl Research Network, but the radiation dosage has
been increased from 45 Gy. The prior study included patients with both
extensive and limited-stage disease, but thoracic radiation was not given to
those with advanced-stage disease. Follow-up for responders (and for stable
limited-disease patients) included oral etoposide for three cycles and then,
for complete responders, prophylactic cranial radiation.

Response rates were high, Dr. Burris noted, 93% in limited disease and 88%
in extensive disease. "The encouraging thing for limited-stage patients is
the high proportion of complete responders— 37%," he observed.
"Adding on the oral etoposide did not seem to convert many patients to
responders." Although three patients with limited disease did go on to
have a complete response after etoposide, he indicated that this might have
been an effect of time.

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