directly affecting Small Cell patients!!

[RandyW]

Higher Chemotherapy Doses No Help in Small-Cell Lung Cancer

By Todd Neale, Staff Writer, MedPage Today

Published: April 09, 2008

Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston.

LAUSANNE, Switzerland, April 9 -- In small-cell lung cancer, increasing the dose intensity of chemotherapy to three times the standard dose did not improve three-year survival, a multicenter, open-label study showed.

Action Points

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Explain to interested patients that the authors of this study recommended abandoning the strategy of intensifying chemotherapy doses to treat small-cell lung cancer after failing to find a benefit over the standard dose.

In a study of 140 patients, there was no difference (P=0.767) in the three-year survival rates between the group receiving a high dose of ifosfamide, carboplatin, and etoposide (18%) and the standard-dose group (19%), Serge Leyvraz, M.D., of University Hospital here, and colleagues found.

There were also no differences in the antitumor response (78% versus 68%, P=0.156) or complete response (39% versus 34%) between the two arms, they reported online in the Journal of the National Cancer Institute.

As expected, toxicity was more severe with the higher dose; all patients in the high-dose group had grade 4 leukopenia and thrombocytopenia and 88% had grade 3/4 anemia.

In the standard-dose group, 70% of patients had grade 3/4 leukopenia and 25% had grade 3/4 thrombocytopenia and anemia.

There were five toxic deaths in the higher-dose group compared with three in patients on the standard dose.

Past studies of the dose intensification of chemotherapy "has subjected patients to clinically significant toxicities without creating a basis for solid conclusions," the researchers said. "With the results of this study, this strategy should now be discarded."

Chemotherapy has improved the prognosis of patients with small-cell lung cancer, but the recurrence rate is high and recurrent tumors are chemoresistant, the researchers said.

For this reason, new approaches such as chemotherapy dose intensification have been explored.

In this study, members of the European Group for Blood and Marrow Transplantation recruited previously untreated patients with small-cell lung cancer and no more than two metastatic sites. Most were male (103 versus 37) and the mean age was 53.

Participants were randomized to a standard dose of ifosfamide, carboplatin, and etoposide or a dose intensified by about three-fold: median dose intensification was 293% (range 174% to 392%) of the standard dose.

The high-dose group also received infusions of previously collected peripheral blood progenitor cells to help control toxicity.

Toxicity was more severe in the high-dose group. Grade 3/4 infections occurred in 6% of standard-dose patients and 31% of high-dose patients.

Non-hematological toxicities, including nausea and vomiting, mucositis, and diarrhea, were more prevalent and severe in the high-dose group.

There was no significant difference (P=0.972) in median progression-free survival between the high-dose group (12.2 months) and the standard-dose group (8.8 months).

Median overall survival did not differ either (18.1 months in the high-dose group versus 14.4 months with the standard dose, P=0.767).

The authors acknowledged that the study was limited by the slow accrual of patients and the fact that the initial trial design had to be modified to include interim analyses.

In an accompanying editorial, Paul Bunn Jr., M.D., of the University of Colorado Cancer Center in Aurora, Colo., wrote that enthusiasm for the researchers' conclusion that intensified doses of chemotherapy should be abandoned "might be tempered by the small sample size and slow accrual … but the data from this study combined with those from other studies should put an end to the era of high-dose 'desperate' therapies."

He added that interest in finding treatments for small-cell lung cancer is waning because of decreasing rates of the disease.

This is unfortunate, he said, because there are a large number of therapeutic targets that still need to be explored, including G-protein-coupled neuropeptide receptors, tyrosine kinase growth factor receptors, and several oncogenes and tumor suppressor genes.

"For the sake of our lung cancer patients," he concluded, "we should strive to obtain funding to move these opportunities to the clinic as rapidly as possible."

The study was funded by unrestricted grants from the Foundation of the Center Pluridisciplinaire. Neither the authors nor Dr. Bunn disclosed any conflicts of interest.

Primary source: Journal of the National Cancer Institute

Source reference:

Leyvraz S, et al "A threefold dose intensity treatment with ifosfamide, carboplatin, and etoposide for patients with small cell lung cancer: A randomized trial"J Natl Cancer Inst 2008; DOI: 10.1093/jnci/djn088.

Additional source: Journal of the National Cancer Institute

Source reference:

Bunn P "Diseases desperate grown"J Natl Cancer Inst 2008; DOI: 10.1093/jnci/djn082.

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