Southwest Oncology Group Trial S9912: Intraperitoneal cisplatin and paclitaxel plus intravenous paclitaxel and pegylated liposomal doxorubicin as primary chemotherapy of small-volume residual stage III ovarian cancer
Introduction
The results of several phase 3 randomized trials have revealed the favorable impact on survival associated with the intraperitoneal, compared to the systemic administration of cisplatin when employed as primary chemotherapy of small-volume residual advanced epithelial ovarian cancer [1], [2], [3], [4]. This outcome led to a decision by the National Cancer Institute to issue a “Clinical Announcement” regarding primary regional therapy in the management of this malignancy [5].
In the most recently reported phase 3 study, which demonstrated a median 16 month improvement in overall survival, paclitaxel was delivered by both the intravenous and intraperitoneal routes [3]. The results of this particular trial stimulated interest in the development of investigative strategies that build upon the foundation of an intraperitoneal cisplatin plus intravenous and intraperitoneal paclitaxel regimen.
Pegylated liposomal doxorubicin has been shown to be biologically active and of clinical utility in platinum and paclitaxel resistant ovarian cancer [6], [7]. An attraction associated with adding this specific agent to a cisplatin/paclitaxel combination is its lack of neurotoxicity [6], [7]. Further, treatment with pegylated liposomal doxorubicin results in a relatively modest degree of bone marrow suppression, certainly compared to other cytotoxic agents commonly employed in this clinical setting [7], [8], [9], [10].
This paper reports the results of a phase 2 front-line ovarian cancer chemotherapy trial conducted by the Gynecology Committee of the Southwest Oncology Group that added systemically-delivered pegylated liposomal doxorubicin to a cisplatin-based intraperitoneal program that also included the administration of both intravenous and intraperitoneal paclitaxel.
Section snippets
Eligibility criteria
Patients considered eligible to enter this multi-center cooperative group phase 2 trial had to satisfy the following criteria: (a) histologically confirmed diagnosis of epithelial ovarian or primary peritoneal carcinoma; (b) previously undergone a staging exploratory laparotomy with an attempt at maximal surgical cytoreduction within 56 days prior to study entry and have optimal residual FIGO stage III disease (largest residual tumor nodule remaining within the peritoneal cavity ≤ 1 cm in
Results
Sixty-eight patients were enrolled on this phase 2 study, of which 5 individuals were subsequently determined to be ineligible. The median age of the treated population was 59 (range 34–80).
Sixty-three patients were evaluable for adverse events (Tables 2A, 2B). There were 5 treatment-related deaths, 4 of which occurred in patients treated with the modified paclitaxel and liposomal doxorubicin regimen after the previously described temporary closure of the study. These deaths resulted from:
Discussion
Several reasonable conclusions can be drawn from the results of this relatively large phase 2 multi-center cooperative group trial that explored the addition of systemically-administered pegylated liposomal doxorubicin to a cisplatin-based intraperitoneal program employed as primary treatment of small-volume residual advanced epithelial ovarian cancer.
First, while the study demonstrated the ability to add pegylated liposomal doxorubicin to a cisplatin-based intraperitoneal chemotherapy program,
Conflict of interest statement
The authors declare that there are no conflicts of interest.
Acknowledgments
This investigation was supported in part by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA32102, CA38926, CA22433, CA46368, CA35431, CA67575, CA12213, CA86780, CA58861, CA13612, CA46113, CA12644, CA35119, CA46441, CA105409 and in part by Alza Corporation (now part of Johnson and Johnson).
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