Friday, July 27, 2007

The Research that Determined it's a No-Go for Marco's Chemo




Adjuvant Chemotherapy Shows No Advantage in Sarcoma, Trabectedin Shows Promise

July 19, 2007 — The largest-ever study of adjuvant chemotherapy in resected soft-tissue sarcoma has failed to show a survival advantage. Patients who underwent intensive treatment with ifosfamide and doxorubicin did not have significantly better outcomes than patients who were followed with observation only, European researchers told the recent American Society for Clinical Oncology (ASCO) 43rd Annual Meeting, in Chicago, Illinois.

The results were presented at the meeting by Penella Woll, MD, PhD, from the University of Sheffield, United Kingdom, on behalf of the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group. The trial involved 351 patients, but 9.5% were ineligible and 4.8% did not receive the allocated treatment, Dr. Woll reported. Patients in both groups of the study underwent radiotherapy if the resection was marginal or if the tumor had recurred. Chemotherapy involved 5 cycles of doxorubicin 75 mg/m2, ifosfamide 5 g/m2 every 21 days, and lenograstim. Of the 175 patients allocated to chemotherapy, 163 started and 127 completed 5 cycles, and 38% had dose reductions or delays, mostly for hematological toxicity or infection.

An interim analysis was performed because survival in the control group was better than expected based on what had been seen in previous studies, Dr. Woll told the meeting. She speculated that this improved survival may be due to better surgery and increased use of adjuvant radiotherapy in this trial compared with those conducted in the past.

Estimated 5-year relapse-free survival was 52% in both groups, and overall survival was 69% in the observational group vs 64% in the chemotherapy group (hazard ratio (HR), 0.621 for both). Thus, the hypothesis that adjuvant chemotherapy improves survival can be rejected, Dr. Woll concluded.

Commenting on this study during a "Highlights-of-the-day" session during the meeting, Robert Maki, MD, PhD, from Memorial Sloan-Kettering Cancer Center, in New York, said that the study showed no advantage for adjuvant chemotherapy. "If there is an advantage to using chemo, it is very small and should be discussed on an individual patient basis."

Experimental New Drug Trabectedin Shows Promise

"We are still looking for better drugs to treat sarcoma," Dr. Maki commented, and he suggested that 1 new contender may be trabectedin (ET-743, Yondelis, PharmaMar/Johnson & Johnson Pharmaceutical Research & Development). He highlighted a study presented at the ASCO meeting in which trabectedin showed clinical benefit in patients with liposarcoma and leiomyosarcoma (L-sarcomas) who had failed on conventional cytotoxics. "When compared with historical controls, the results indicate activity for this novel compound," Dr. Maki commented, although he added that the response rate was low.

Trabectedin is an experimental drug, based on a compound originally found in the sea squirt, which is being developed for use in sarcomas as well as ovarian and prostate cancers. The product is awaiting approval in Europe for use in sarcomas and has orphan-drug designation in both Europe and the United States for use in sarcomas as well as in ovarian cancer.

The study presented at the ASCO meeting was a phase 2 trial sponsored by the manufacturers, involving 270 patients, all of whom had progressive L-sarcomas despite treatment with anthracyclines and ifosfamide and additional agents in the majority of cases. The trial compared 2 regimens of trabectedin, given either as 1.5 mg/m2 by intravenous (IV) infusion over 24 hours every 3 weeks (24-hour group) or 0.58 mg/m2 by IV infusion over 3 hours given weekly (3-hour group) in a 28-day cycle.

The results favored the 3-hour-infusion administration schedule. In a protocol-specified primary analysis, this 3-hour group had a statistically significant 27% reduction in the risk for disease progression (HR, 0.734; P = .0302). The median time to progression in this group was 3.7 months, vs 2.3 months in the 24-hour group. Secondary end points included median progression-free survival, which was 3.3 months in the 3-hour group vs 2.3 months in the 24-hour group (HR, 0.755; P = .0418), and median survival, which was 13.8 months vs 11.8 months (HR, 0.823; P = .1984), respectively.

The researchers concluded that both dosing regimens were efficacious, but "there appears to be superior disease control" with the 3-hour-infusion regimen. They also commented that the 3-hour-infusion schedule was associated with "somewhat more neutropenia and transaminitis without clinical consequences," and no cumulative toxicities were apparent in either group. In a press release, PharmaMar commented that this study confirms the safety profile of trabectedin, with transaminase elevations, emesis, and fatigue being the most common adverse events reported.

Zosia Chustecka for Medscape

American Society for Clinical Oncology 43rd Annual Meeting: Abstracts 10008 and 10060. Presented June 4 and June 3, 2007.

NOTE: The presentation at the ASCO conference will be available to public in September. I'll post it when its available!

1 comment:

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