Efficacy of Oral Etoposide Among Patients With Recurrent or Refractory Epithelial Ovarian Cancer

The administration of oral etoposide at a dose of 50 mg/m² showed fairish oncologic outcomes with manageable toxicity among patients with recurrent or refractory epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer (J Obstet Gynaecol. 2022; 1-5. doi:10.1080/01443615.2022.2049724)

For recurrent or refractory epithelial ovarian cancer that is resistant to platinum-based chemotherapy, out-patient treatment with oral etoposide can provide palliation, control symptoms, and enhance quality of life while offering a response rate similar to that of several other chemotherapy regimens. Moreover, because of its route of administration, oral etoposide has an advantage over these other regimens. 

To evaluate the effectiveness of oral etoposide recurrent or refractory epithelial ovarian, primary peritoneal, and fallopian tube cancer, Chompunoot Kongsawatvorakul, MD, Department of Obstetrics & Gynaecology, Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, and colleagues collected data on patients with these cancers who received oral etoposide, 50 mg/m² at Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, from January 1997 to December 2017. The primary outcome of this retrospective study was progression-free survival (PFS), and the secondary outcome was overall survival (OS).

About half of the study patients were treated with oral etoposide as third-line chemotherapy, and the study included 13 patients who received only one cycle of oral etoposide.

After analyzing the medical records of 66 patients, the researchers found that their median PFS was 3.1 months (95% CI, 2.3 mo to 3.9 mo), and their median OS was 8.3 months (95% confidence interval [CI], 6.8 mo to 10.4 mo). Moreover, one patient had a complete response to oral etoposide therapy. 

The researchers also found that the following factors were not associated with prognosis: age, body mass index, histopathologic subtype, primary treatment, result of the primary surgery, platinum status, site and size of the recurrent cancer, treatment after discontinuation of oral etoposide, and line of chemotherapy regimen. The only independent factor that signaled a poor prognosis was the initial stage of the cancer.

Regarding histopathologic subtypes, two-thirds of the study patients had serous carcinoma and clear cell carcinoma. Based on the results of previous studies, the study authors hypothesized that clear cell carcinoma has a worse prognosis than serous papillary carcinoma.

Regarding adverse effects, grade III or IV neutropenia developed in 9 of the 66 study patients, or 14%. These adverse effects resulted in dose delay in 36% of study patients and dose reduction in 17%. Although no patients died of neutropenia, about one-quarter of the patients in the study discontinued oral etoposide owing to adverse effects.

“In conclusion, administration of oral etoposide at a dose of 50 mg/m² showed fairish oncologic outcomes,” wrote Dr Kongsawatvorakul and colleagues, adding, “It is an option for the palliative aim in platinum resistant patient who refused intravenous chemotherapy, and the toxicity profile is also manageable.”

“Future prospective trials should be performed with more sample size and focusing on other aspects such as assessment of the quality of life,” Dr. Kongsawatvorakul and team recommended. “The future research question might be on whether a lower dose will have a comparable outcome and a lower side effect,” they added. 

Another option for platinum-resistant or -refractory ovarian cancer is combining oral etoposide with another anti-cancer agent. For example, the authors noted that, in the AEROC trial in patients with this cancer, this combination resulted in a 54% response rate.