EORTC Endometrial Ca Trial Challenges Findings From GOG

LISBON, Portugal--Doxorubicin coupled with cisplatin (Platinol)confers a distinct survival edge over the anthracycline alonein women with advanced inoperable or recurrent endometrial carcinoma,according to the latest findings of the Gynaecological CancerCooperative Group (GCCG) of the European Organization for Researchand Treatment of Cancer (EORTC).

The results of this new EORTC trial mount a direct challenge tothe contrasting data recently reported by the Gynecological OncologyGroup (GOG), said Dr. Matti S. Aapro, of the European OncologyInstitute, Milan, and Clinique de Genolier, Switzerland.

Speaking at the congress of the European Society of Medical Oncology,Dr. Aapro described candidates for the EORTC trial as women withmeasurable, pathologically proven lesions in nonirradiated areaswho had received no prior chemotherapy and had good performancestatus. Over the last 6 years, he said, more than 160 such womenhave been randomized to receive either doxorubicin, 60 mg/m²,plus cisplatin, 50 mg/m², every 4 weeks, or the same doseof doxorubicin alone every 4 weeks.

The combination regimen was not without serious drawbacks, Dr.Aapro acknowledged, citing a 47% incidence of severe neutropenia(versus 32% with doxorubicin alone), an 11% incidence of severethrombocytopenia (versus 6% for single-drug therapy), and a 38%incidence of nausea and vomiting (versus 14% for doxorubicin alone).

On the other hand, although the rate of study discontinuationdue to drug toxicity was greater in the combination therapy group,the rate of withdrawal because of disease progression was strikinglyhigher among women treated with doxorubicin alone.

Complete responses were observed in 10 (17%) of 59 eligible womenin the combination arm, compared with 6 (11%) of 54 in the single-agentarm, and partial responses were documented in 17 (29%) of thecombination therapy patients but in only 3 (6%) of those on doxorubicinalone. No change was discerned in 13 (22%) of the patients receivingdoxorubicin plus cisplatin and in 12 (22%) of the women treatedwith doxorubicin alone.

Longer Duration of Survival

Although the duration of response in the nine women who respondedto single-drug therapy was longer (18.5 months) than that in thecombination therapy group (10.5 months), Dr. Aapro stressed thatthis difference did not reach statistical significance, sinceso few patients responded to doxorubicin alone.

"The duration of survival was longer in the combination armat 12.1 months, as compared with 6.8 months in the single-agentarm," he said. "In an intention-to-treat analysis thisdifference is still statistically significant at P = .04."

"Our conclusion," Dr. Aapro said, "is that theaddition of cisplatin to doxorubicin in the dose and scheduleused in this study provides a significant survival advantage inpatients treated for advanced or recurrent endometrial cancer."

He suggested that the failure of the GOG trial to reveal a similarbenefit may have stemmed from the greater intensity of therapyused in that study. Anticipating a more elderly population thanthey actually accrued, the EORTC group had opted for 4-week ratherthan 3-week intervals between chemotherapy cycles.