Weekly regimen not optimal for cisplatin: the finding is important, because about 5 years ago the weekly regimen became the standard of care

OB/GYN News, May 15, 2006 by Doug Brunk

PALM SPRINGS, CALIF. -- Women with cervical cancer who received weekly cisplatin treatment had significantly worse progression-free survival rates and significantly worse toxicity than did those who received cisplatin 5 days in a row every 21 days, according to results of a long-term, single-site, retrospective study.

The finding is important, because about 5 years ago the weekly regimen became the standard of care, due primarily to the ease of weekly dosing and the lower cost of outpatient administration, Dr. Mark Einstein said in an interview at the annual meeting of the Society of Gynecologic Oncologists.

"In the past we used to do an inpatient infusional dosing of cisplatin concomitant with radiation therapy for the treatment of locally advanced cervical cancer," he explained. "In 2001 there was a switch over to outpatient weekly regimens, but there was never really a trial to show that the [outcomes] are the same between the two patient regimens."

He and his associates studied 77 consecutive patients with stages IB2-IV cervical cancer who were treated with cisplatin concomitant with external mean radiotherapy and two 9-Gy high-dose-rate brachytherapy insertions at the Monte-fiore Medical Center of the Albert Einstein College of Medicine, Bronx, N.Y., between 1995 and 2004. The 50 women in the 5-day treatment group received cisplatin 20 mg/[m.sup.2] for 5 days every 21 days with concomitant radiotherapy. The 27 women in the weekly treatment group received 40 mg/[m.sup.2] weekly with concomitant radiotherapy.

Nearly half of the women in the 5-day treatment group (48%) had stage III or IV disease, compared with 26% of women in the weekly treatment group. The rest of the women had stage IB2 or II disease. The median follow-up was 42 months.

Dr. Einstein, a gynecologic oncologist with the Albert Einstein College of Medicine, reported that there were no significant differences between the two treatment groups in terms of age, race, histology, body mass index, anemia, and total radiotherapy doses.

Overall, 3-year progression-free survival was 81% for the 5-day treatment group, compared with 66% for the weekly treatment group, a difference that was statistically significant.

After the researchers adjusted for cancer stage, patient age, and completion of treatment, women in the weekly treatment group were 3.5 times more likely to fail treatment than were their counterparts in the 5-day treatment group. Similarly, women in the weekly treatment group were 2.7 times more likely to die from cervical cancer than were those in the 5-day treatment group.

Dr. Einstein also reported that women with late-stage disease who received weekly treatment were 3.43 times more likely to develop acute toxicity--primarily in the GI tract--compared with their counterparts in the 5-day treatment group. "That's probably [because the 5-day group] got a lot more fluids when the patients were in the hospital, while they were getting their chemotherapy," he speculated. "But that difference is hard to glean out."

Dr. Einstein emphasized that a multicenter, randomized, controlled trial is needed to confirm the findings. He and his associates are working on such a trial design and may add a third treatment arm of women who receive sustained low-dose cisplatin throughout their radiation therapy. "The idea [is] that with the 5-day infusion, they're getting a relatively sustained dose once every 3 weeks," he said. "Maybe it's that sustained dose that's improving the survival benefit."

BY DOUG BRUNK

San Diego Bureau