Treatment of advanced ovarian cancer with intraperitoneal (IP) chemotherapy resulted in a significant improvement in long-term progression-free survival (PFS) and overall survival (OS) compared with intravenous (IV) chemotherapy, according to a study published in the Journal of Clinical Oncology.1

For this post hoc analysis, data were pooled from 876 patients enrolled in Gynecologic Oncology Group (GOG) protocols 114 or 172.

Patients with stage III epithelial ovarian or peritoneal carcinoma were eligible if they had no residual disease greater than 1 cm after surgery and had a GOG performance status of 0 to 2.


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In GOG 114, patients were randomly assigned to receive IV paclitaxel 135 mg/m2 followed by 6 courses of IV cisplatin 75 mg/m2 or 2 courses of IV carboplatin followed by IV paclitaxel 135 mg/m2 on Day 1 and 6 courses of IP cisplatin 100 mg/m2 starting on Day 8.

For GOG 172, all patients received IV paclitaxel 135 mg/m2 and were then randomly assigned to receive IV cisplatin 75 mg/m2 on Day 2 or IP cisplatin 100 mg/m2 on Day 2 followed by 6 cycles of IP paclitaxel 60 mg/m2 beginning on Day 8.

In the pooled analysis, with a median follow-up of 10.7 years, IP chemotherapy resulted in a median PFS of 25 months compared with 20 months in the IV arm (adjusted HR, 0.79; 95% CI, 0.67 to 0.92; log-rank P = 0.003).

In addition, median OS was prolonged by 10.4 months in the IP chemotherapy arm (61.8 versus 51.4 months; adjusted HR, 0.76; 95% CI, 0.65 to 0.90; log-rank P = 0.002).

Gross residual disease was associated with a 1.89-fold increase in the risk of death compared with patients who had no visible disease (95% CI, 1.48 to 2.43; P < 0.001).

No visible disease, serous rather than clear-cell/mucinous histology, and 6 cycles of IP chemotherapy rather than fewer cycles and cross-over to IP therapy were associated with better rates of long-term survival.

However, the discontinuation rate of IP chemotherapy was 50% in the GOG protocols, and completion of 6 cycles of IP therapy was associated with a survival advantage compared with patients who completed 3 cycles or less.

RELATED: Intraperitoneal Chemotherapy Improves Survival in Ovarian Cancer

In the post hoc analysis, each cycle of IP chemotherapy completed conferred a 12% reduction in the risk of death (adjusted HR, 0.88; 95% CI, 0.83 to 0.94; P < 0.001).

Younger age, but not demographic or clinicopathologic factors, was associated with completion of 6 cycles of IP therapy.

In an accompanying article,2 Michael A. Bookman, MD, of Arizona Oncology in Tucson, AZ, and Mark F. Brady, MD, of Baptist Memorial Health Care in Memphis, TN, commented that the survival benefit observed in patients who received the full 6 cycles of IP therapy, “could easily be explained by clinical factors such as self-selected patients with a more favorable prognosis, regardless of the number of cycles actually administered.”

In addition, more data are needed to definitively determine if 6 cycles of IP chemotherapy provides a greater benefit compared with 3 cycles. Therefore, Dr. Bookman and Dr. Brady suggested that, “Patients should be managed in accordance with their individual tolerance and treatment-related toxicity.”

References

  1. Tewari D, Java JJ, Salani R, et al. Long-term survival advantage and prognostic factors associated with intraperitoneal chemotherapy treatment in advanced ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. March 23, 2015. [Epub ahead of print] pii: JCO.2014.55.9898.
  2. Bookman MA, Brady MF. Intraperitoneal chemotherapy: long-term outcomes revive a long-running debate. J Clin Oncol. March 23, 2015. [Epub ahead of print] pii: JCO.2014.60.2797.