Read this today: Radiation 'Sandwiched' Twixt Chemo Cycles Combats Endometrial Cancer (UPSC particul

Someone else may have already posted this, & a lot of it is verification of the Yale study from long ago, but it just hit OncologySTAT this week:

Radiation 'Sandwiched' Twixt Chemo Cycles Combats Endometrial Cancer
Elsevier Global Medical News. 2011 Mar 14, D McNamara

ORLANDO (EGMN) - Adjuvant radiation therapy that was "sandwiched" between chemotherapy cycles of paclitaxel and carboplatin is "highly efficacious" in women with completely resected uterine papillary serous carcinoma, investigators reported, based on results of a prospective, phase II study.

"We noted a particularly high survival rate more than 50% at 3 years in stage III and IV patients who had no visible disease after surgery," Dr. Mark H. Einstein said at the annual meeting of the Society of Gynecologic Oncologists.

A total of 78 evaluable patients with histologically confirmed uterine papillary serous carcinoma (UPSC) began a regimen of three cycles of paclitaxel and carboplatin, followed by adjuvant pelvic radiation therapy, and then a subsequent three cycles of the same chemotherapy. Most women (82%) had stage I or II cancer (confined to the uterus), and the remaining 18% had stage III or IV disease.

Of the 78 women who started treatment, 72 completed the first three cycles and had some radiation, 67 completed prescribed radiation therapy, and 65 completed the full prescribed regimen, Dr. Einstein said.

Survival analysis was performed on the group of 72 patients. Median overall progression-free survival was 65.5 months for stage I and II disease, Dr. Einstein said. The overall progression-free survival for advanced disease with no gross evidence of disease after surgery was 25.8 months.

Median overall survival was 76.5 months for stage I and II patients and 35.9 months for the advanced stage patients. A calculated 3-year survival probability was 84% for women with stage I and II cancer and 50% for those with stage III and IV disease.

All study participants were treated during 1999-2010 at Albert Einstein College of Medicine/Montefiore Medical Center in the Bronx, N.Y., where Dr. Einstein is a gynecologic oncologist.

Enrollment took longer than 10 years, during which time there were changes in radiation therapy - a potential study limitation, said invited discussant Dr. Paola Alvarez Gehrig.
Nonetheless, this study is important, Dr. Gehrig said, because evidence-based guidelines for UPSC are limited. Also, a search for effective treatment is laudable because UPSC "is a rare but aggressive subtype of endometrial cancer." Although it represents 10% of endometrial cancer cases, UPSC accounts for up to 40% of endometrial cancer deaths (Brit. J. Cancer. 2006;13:642-6), the University of North Carolina at Chapel Hill.

The regimen consisted of paclitaxel at 175 mg/m2 and cisplatin (AUC [area under the curve] = 6) every 21 days for three cycles. Radiation treatment consisted of brachytherapy, external-beam radiation, or both, based on cancer stage and physician discretion. A total of 55 women had both therapies, 4 had brachytherapy alone, and 6 had external-beam radiation alone. The radiation field was extended for women with N2-positive pelvic disease or positive para-aortic nodes. The additional three cycles were paclitaxel at the same dose plus cisplatin (AUC = 5-6) every 21 days.

Median age was 68 years. Participants were 54% black, 41% white, 2.5% Asian, and 2.5% other. In terms of ethnicity, the cohort was 19% Hispanic and 81% non-Hispanic.

Based on these results, the researchers proposed that this "sandwiched" regimen be considered as an arm for future phase III clinical trials that assess patients with UPSC.

Toxicities were reported for the 78 patients who initiated therapy. Toxicity-associated dose delays and reductions primarily occurred after radiation therapy, Dr. Einstein said. "Only about 40% of these occurred before radiation therapy." Doses were reduced for 26 cycles (6.0% of 435 total chemotherapy cycles administered), and 37 cycles (8.5%) were delayed because of toxicities.

Grade 3 hematologic toxicities were noted in 62 cycles (14% of total) and grade 4 toxicities in 56 cycles (13%); neuropathy was the most common, followed by thrombocytopenia and anemia. Of the 16 grade 3 and 4 nonhematologic effects, infections (5), neuropathy (4), and deep vein thrombosis (3) were the most commonly reported. No participants died because of treatment.
The single-center study design is a potential limitation, Dr. Einstein said. In addition, although all women with stage III or IV had omental sampling, only 63% of early-stage women did, so some women may have been misclassified, he said.

The current findings build on a previous pilot study by Dr. Einstein and his colleagues. They demonstrated "excellent survival" among 30 women with no gross disease after initial staging surgery using a similar regimen (Gynecol. Oncol. 2008:108:201-6). "Based on the success of our pilot study, we expanded on the study with longer follow-up and toxicity assessment," Dr. Einstein said. Cisplatin dosing was lowered from the pilot study (initially up to 7.5 AUC) to reduce toxicity potential. "We've improved the protocols."

Other investigators have assessed various sequencing of chemotherapy and radiation. For example, in a study of 109 women with advanced endometrial cancer, 45 treated with chemotherapy followed by radiation and then more chemotherapy experienced improved survival compared with 46 who received chemotherapy and then radiation or the 18 who received radiation and then chemotherapy (Gynecol. Oncol. 2009;114:442-7).

Other researchers found "decent" progression-free survival and low recurrence rates, Dr. Einstein said, when 43 women with advanced endometrial cancer were treated with a regimen of four cycles of chemotherapy, then external-beam radiation, and then two more cycles of chemotherapy (Gynecol. Oncol. 2009;114:94-98).

Dr. Einstein and Dr. Gehrig said that they had no relevant disclosures.