Dose-Dense Adjuvant Chemotherapy Shows Potential in Endometrial Cancer

Liron Kogan, MD

Dose-dense chemotherapy could be a superior option for adjuvant treatment of endometrial cancer compared with standard chemotherapy, according to findings from investigators with Segal Cancer Center at Jewish General Hospital in Montreal.

A dose-dense regimen of paclitaxel plus carboplatin was associated with improved overall survival (OS; P =.05), superior progression-free survival (PFS; P = .003), and significantly fewer distant metastases.

“Our results indicate that shifting from a three-weekly standard treatment to dose dense paclitaxel while maintaining carboplatin every 3 weeks as adjuvant treatment in high and intermediate-high-risk EC patients, prolongs PFS,” first author Liron Kogan, MD, Division of Gynecologic Oncology, Jewish General Hospital, and coinvestigators wrote.

The results come from a retrospective cohort study comparing consecutive patients with high and intermediate-high risk endometrial cancer with a nonoverlapping historical cohort with similar characteristics. The former group was treated with paclitaxel and carboplatin in a dose-dense protocol, and the latter received chemotherapy over the standard 3-week protocol.

Patients who were diagnosed and treated after their surgery for endometrial cancer at Segal Cancer Center from 2008 to 2015 were included in the study (N = 512).

All patients in both cohorts underwent hysterectomy, bilateral salpingo-oophorectomy and surgical staging. Patients who had surgery from January 2008 to October 2010 underwent complete pelvic lymphadenectomy. After October 2010, patients underwent sentinel lymph node mapping in addition to complete pelvic lymphadenectomy.

The mean age of patients in the study was 66.1 years and there was no statistical difference between the 2 groups (P = 0.9). Clinical characteristics including BMI, stage, histological type and grade were not significantly different between the 2 groups. In total, 63 patients (51.6%) were diagnosed with advanced stage disease (III—IV), including 7 patients with stage IVb disease.

Fifty-four patients (88.5%) in the standard cohort completed the planned 6 courses of treatment compared with 59 (96.7%) in the experimental group (P = .16).

ECOG status during the treatment was similar between the 2 groups (P = 0.63). Nine patients (14.8%) who were treated with the standard regimen underwent dose reductions or delays due to toxicities compared with 20 patients (32.8%) in the dose-dense group (P = .03).

After adjusting for age, FIGO stage, grade, histological type and ASA score, the difference between groups remained unchanged in terms of PFS (hazard ratio [HR], 0.4; 0.2-0.8; P =.01), but did not reach statistical significance for OS (HR, 0.5; 0.2-1.2; P = .12). FIGO stage and grade were independent predictors of PFS.

That said, Patients with advanced FIGO stage in the dose dense group had a significantly better OS than those in the standard protocol. PFS was also improved in the [dose-dense] cohort for both early (P = .03) and advanced stage disease (P = .008), for endometrioid (P = .02) and nonendometrioid tumors (P = .03), and for high-grade tumors (P = .009).

“Overall, the [dose-dense] protocol might be superior to standard treatment in patients with endometrial carcinoma, but requires more visits for the patients, and is more labor and cost intensive,” researchers wrote. “While our study suggests that [dose-dense] treatment might be preferable, a randomized prospective trial would further clarify our findings.”

Overall, 86 patients (70.5%) experienced some type of drug-related toxicity. The rates of gastrointestinal, hematologic, neurologic, and dermatologic side effects were similar between the treatment groups. Musculoskeletal side effects were more frequent in the standard therapy cohort (27.9% vs 6.6%; P = .005).

Until Sep 27, 2016, 29 patients progressed and 24 deaths occurred in the standard therapy cohort, compared with 11 progressions and 9 deaths in the [dose-dense] cohort. At 42 months, which represents the median follow-up in the experimental cohort, twice as many patients in the standard group progressed (18 vs 9) and more than twice as many died (17 vs 7).

Kogan L, Laskov I, Amajoud Z, et al. Dose dense carboplatin paclitaxel improves progression free survival in patients with endometrial cancer. Gynecol Oncol. 2017;147(1):30-35. doi:10.1016/j.ygyno.2017.07.134.