Evaluation of toxicities related to novel therapy in clinical trials for women with gynecologic cancer

• Published in: Cancer Vol. 126; no. 10; pp. 2139 - 2145
• Main Authors: Lee, Yeh Chen, Wang, Lisa, Kohn, Elise C., Rubinstein, Lawrence, Ivy, S. Percy, Harris, Pamela J., Lheureux, Stephanie
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 15.05.2020
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Cancer; Cancer therapies; Chemotherapy; clinical protocols; Clinical trials; Clinical Trials, Phase I as Topic; Databases, Factual; Demographics; Demography; drug therapy; Drug-Related Side Effects and Adverse Reactions - classification; Drug-Related Side Effects and Adverse Reactions - epidemiology; Female; Genital Neoplasms, Female - drug therapy; Health risks; Health services; Humans; Medical treatment; Middle Aged; Multiple regression models; National Cancer Institute (U.S.); Oncology; Ovarian cancer; ovarian neoplasms; Patients; Peritoneal diseases; Peritoneum; Radiation therapy; Regression analysis; Retrospective Studies; Surgery; Toxicity; United States; Young Adult; United States; toxicity; ovarian neoplasms; drug therapy; clinical protocols
• DOI: 10.1002/cncr.32783
• ISSN: 0008-543X

Background Women with gynecologic cancer may be at increased risk for adverse events (AEs) due to peritoneal disease burden and prior treatment (surgery, chemotherapy, and pelvic radiotherapy). This study compared the toxicity profiles of patients with and without gynecologic cancer enrolled in phase 1 trials. Methods This was a retrospective analysis of the National Cancer Institute phase 1 database for all trials enrolling 1 or more patients with gynecologic cancer over 2 decades (1995‐2015). Clinical parameters collected included demographics, cancer history, trial information, AEs, and responses. AEs (according to the Common Terminology Criteria for Adverse Events) were documented for each patient during treatment, and they were counted once and analyzed on the basis of the highest grade and drug attribution. Multiple regression models were used to compare AEs at the baseline and during treatment. Results A total of 4269 patients enrolled in 150 trials were divided into 3 groups: 1) women with gynecologic cancer (n = 685), 2) women with nongynecologic cancer (n = 1698), and 3) men with cancer (n = 1886). The median age was 58 years. The mean number of total AEs reported during treatment was highest for women with gynecologic cancer (17.1 vs 14.7 vs 13.5; P < .001), even though they were similar at the baseline (7.0 vs 7.4 vs 7.0; P = .09). The mean number of drug‐related AEs was also highest for women with gynecologic cancer (8.3 vs 6.9 vs 6.2; P < .001). Grade 3 to 5 AEs were similar (2.3 vs 2.3 vs 2.1); however, grade 2 AEs were more frequent in women with gynecologic cancer (4.6 vs 3.9 vs 3.5). Treatment discontinuations due to AEs were similar (9% vs 9% vs 10%). Conclusions Women with gynecologic cancer experienced more frequent low‐grade AEs during treatment, and this warrants attention to support their symptom burden. Study dose management should be considered for recurrent grade 2 AEs, particularly during continuous therapy. Compared with women with other solid tumors, women with gynecologic cancer who are enrolled in phase 1 trials experience more frequent and predominantly grade 2 adverse events during treatment. Specific attention is warranted during continuous therapy to support their symptom burden and to incorporate management for recurrent grade 2 adverse events.