Pilot Phase 2 Trial of 4 Months of Maintenance Pegylated Liposomal Doxorubicin in Patients with Advanced Ovarian Cancer after Complete Response to Platinum and Paclitaxel-Based Chemotherapy

Abstract

Background/Aims: Stages III and IV ovarian and peritoneal cancer patients are commonly treated with combination chemotherapy after surgical debulking. This phase II trial investigated the use of pegylated liposomal doxorubicin as consolidation chemotherapy for these patients. Methods: Women with stage III or IV ovarian or primary peritoneal carcinoma demonstrating no clinical evidence of disease after primary therapy were eligible for enrollment. Patients received 4 cycles of 40 mg/m² IV of pegylated liposomal doxorubicin every 28 days. Results: Twelve patients were enrolled. There were 6 stage IIIC and 6 stage IV patients. Ten patients received 4 cycles. Two patients had dose limiting skin toxicity manifest as hand–foot syndrome and received only 3 cycles. Forty-six of a planned 48 cycles were administered. Median disease-free survival from registration is 10 months with a mean of 18 months. Median overall survival has not yet been reached. Four patients are disease-free, two have relapsed and six have died from disease progression. Conclusion: Pegylated liposomal doxorubicin is a well-tolerated choice for consolidation chemotherapy in patients with ovarian or primary peritoneal carcinoma.

Improved Overall Survival with 12 Cycles of Single-Agent Paclitaxel Maintenance Therapy following a Complete Response to Induction Chemotherapy in Advanced Ovarian Carcinoma

“…Several varying attempts at designing an optimal maintenance therapy regimen to prolong PFS and OS in ovarian cancer have been investigated with limited success [12,16,17]. Despite the PFS benefits observed in the SWOG/GOG phase 3 trial [7,8], researchers and clinicians have been skeptical of maintenance chemotherapy because of the unproven impact on OS [8,16,12].…”

“…In a recent phase 3 trial involving paclitaxel maintenance chemotherapy, ovarian cancer patients who had a complete response to primary chemotherapy did not exhibit PFS or OS benefits [12]. Moreover, studies have expressed concern that in spite of any perceived therapeutic advantage, the treatment is associated with adverse patient toxicity and a potentially unfavorable impact on quality of life [16,17,18]. Therefore, in order to substantiate the benefits of maintenance chemotherapy on patient OS, studying a standard relatively well-tolerated regimen with prolonged follow-up may provide meaningful input for this highly clinical and relevant debate.…”

Clinical Utility of CA-125 for Maintenance Therapy in the Treatment of Advanced Stage Ovarian Carcinoma

“…Maintenance therapy is one strategy that has been hypothesized to have a realistic potential to improve survival in patients who have demonstrated initial chemosensitivity to the initial 5 to 6 cycles of primary chemotherapy. 20 Currently, although there are data strongly supporting this approach, the overall concept remains controversial. 21 Previous studies have suggested that the CA-125 serum level may be of clinically relevant value in defining which patients have the greatest potential to benefit from maintenance therapy.…”

Intraperitoneal Paclitaxel as Consolidation Treatment in Ovarian Cancer Patients: A Case Control Study

“…As to intravenous consolidation chemotherapy, most of the published studies did not observe any advantage in terms of survival. In particular, drugs used intravenously were topotecan [25], epidoxorubicin [26], pegylated liposomal doxorubicin [27,28] and platinum plus paclitaxel [29] given for an additional 3–4 cycles after completion of standard adjuvant chemotherapy.…”