Irinotecan hydrochloride (CPT-11) and mitomycin C as the first line chemotherapy for ovarian clear cell adenocarcinoma
Introduction
Ovarian clear cell carcinoma (OCCA) was originally termed mesonephroid by Schiller in 1939 as it was thought to originate from mesonephric structures and seemed to resemble renal cell carcinoma [1]. However, in 1967, Scully and Barlow noted the frequent association of clear cell carcinomas with endometriosis and endometrioid carcinoma of the ovary, suggesting a mullerian origin [2]. In 1973, the World Health Organization recognized clear cell carcinoma as a distinct type of epithelial ovarian neoplasm [3]. Many gynecologic oncologists seem to feel that OCCA is somehow different from other subtypes of epithelial ovarian cancer, and they sometimes express disappointment with the treatment results in OCCA patients.
The introduction of cisplatin-based chemotherapy in the late 1970s markedly changed the postoperative management of ovarian cancer patients. Nonetheless, the results and value of these efforts and therapies applied to OCCA are as yet undetermined [4], [5], [6], [7]. Crozier et al. [8] found no differences in progression-free interval or survival of OCCA patients among 17 patients not treated with chemotherapy, 19 treated with platinum-containing regimen, 18 treated with single agents, and 5 treated with nonplatinum-containing combinations. In the study by Goff et al. [6], overall, 70% of the 23 evaluable patients with stage III OCCA showed progression of disease while on platinum-based chemotherapy, which is significantly different from 29% rate of progressive disease observed in patients with papillary serous carcinoma. Other reports also indicate that OCCA has very low sensitivity to platinum-based chemotherapy [9], [10]. Recently, Sugiyama et al. examined the clinical response to platinum-based chemotherapy in patients with measurable residual OCCA. Patients with OCCA showed a very low response rate of 11.1% (3 of 27), but a high incidence rate of progressive disease (PD) (22 of 27; 81.5%), whereas patients with serous subtype had a high response rate of 72.5% (79 of 109) and a low incidence rate of PD (20 of 109; 18.3%), a difference that was apparently significant [11]. Similarly, the only previous study to date on the subject by Goff et al. reported a higher rate of incidence of PD with platinum-based chemotherapy in OCCA patients with measurable or nonmeasurable disease (16 of 23; 70%) compared with serous subtype patients (10 of 34; 29%) [6]. Another group of authors demonstrated that platinum-based chemotherapy did not appear to improve the survival of patients with OCCA compared with the survival from nonplatinum-based chemotherapy [12]. There are no reports indicating that any patient with pure OCCA shows an appreciable response to platinum-combination chemotherapy.
Several reports demonstrated to establish the treatment for OCCA using irinotecan hydrochloride (CPT-11). In vitro study, SN-38 (the active metabolite of CPT-11) was reported to be the most effective agent, followed by MMC, while there was considerable resistance to cisplatin [13]. The efficacy of CPT-11 and mitomycin C (MMC) combination chemotherapy (CPT-M) had been reported to demonstrate significant activity in patients with platinum-refractory OCCA or mucinous adenocarcinoma [14], [15]. The purpose of this study was to report the results of adjuvant CPT-M for OCCA.
Section snippets
Patients and methods
This was a nonrandomized trial. Women with OCCA who underwent primary debulking surgery between 1996 and 2002 at Niigata University hospital were entered into this trial. Eligibility criteria for this trial included the following. All patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≦2, adequate hematologic (WBC count, 4000/μl to 10,000/μl; absolute neutrophil count, ≧2000/μl; hemoglobin, ≧9.0 g/dl, and platelet count, ≧100,000/μl), hepatic
Patient characteristics and treatment summary
Between April 1996 and December 2002, twenty patients were enrolled into this trial at Niigata University Hospital (CPT-M group). All patents were evaluable for toxicity. Pretreatment characteristics are shown in Table 1. The median age was 51 years (range, 29–74 years). Twelve patients were in stage Ic, 1 in stage IIa, 5 in stage IIc, 1 in stage IIIc, and 1 in stage IV. Optimal cytoreduction (residual disease less than 1 cm) with their initial surgery was obtained in all 20 patients. In our
Discussion
Currently, no anticancer agents are definitively effective for OCCA based on large-scale clinical studies, and the mechanism of resistance to chemotherapy in OCCA is not well understood. Several reports demonstrated to establish the treatment for OCCA using CPT-11. Shimizu et al. performed sensitivity tests of anticancer agents using OCCA cell lines, demonstrating that SN-38 (the active metabolite of CPT-11) was the most effective agent, followed by MMC, while there was considerable resistance
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Cited by (27)
The elevated risk of ovarian clear cell carcinoma among Asian Pacific Islander women in the United States is not affected by birthplace
2020, Gynecologic OncologyCitation Excerpt :However, due to a lack of more effective agents, platinum-based therapy remains first-line treatment. Numerous case reports supported the efficacy of irinotecan as a possible treatment for OCCC [11,12]. JGOG 3014 found no significant difference in progression-free survival, but subset analysis of patients without residual disease showed longer, though not significant PFS [13].
Clear cell carcinoma of the ovary: A review of the literature
2012, Gynecologic OncologyCitation Excerpt :Ovarian CCC tumors tend to present at earlier stages. In large institutional series, comparing early (I/II) vs late (III/IV) stage EOC, 47–81% of CCC tumors were diagnosed at early stages [7,11,59,61,63–65]. For example, in the study by Rauh-Hain et al., inclusive of 121 patients with ovarian CCC, and one of the largest in the literature, Stages I and II were reported in 48.4% of patients at initial diagnosis [62].
Prognosis of ovarian clear cell carcinoma compared to other histological subtypes: A meta-analysis
2011, Gynecologic OncologyCitation Excerpt :However, clinical studies using this regimen have included only a small percentage (2%) of patients with CCC, and thus standard chemotherapeutic regimens for CCC are not yet determined. Recently, studies on irinotecan-based regimens in CCC have shown promising results [40,41] and randomized trials now underway [42]. One of the potential limitations of this meta-analysis is that about 2/3 of patients' data comes from a single study and there was a lack of central pathology review in that study [11], which might have affected the final results of this study.
Do clear cell ovarian carcinomas have poorer prognosis compared to other epithelial cell types? A study of 1411 clear cell ovarian cancers
2008, Gynecologic OncologyCitation Excerpt :To our knowledge there are no randomized clinical trials that have definitively shown that different treatment regimens for clear cell cancers of the ovary versus other epithelial cell types can improve survival outcomes. However, there are many retrospective series that have reported on the potential benefit of various chemotherapeutic combinations[19–21]. Recently, our group has proposed a clinical trial using novel targeted agents against VEGF (vascular endothelial growth factor) and PDGF (platelet-derived growth factor) in the treatment of recurrent and persistent ovarian clear cell cancers.
Phase II study of sequentially administered low-dose mitomycin-C (MMC) and irinotecan (CPT-11) in women with metastatic breast cancer (MBC)
2008, Annals of OncologyCitation Excerpt :Although uridine diphosphate glucuronosyltransferase (UGT)1A1 polymorphism was not tested, it is of interest to speculate whether some of these pts were homozygous or heterozygous for UGT1A1*28 alleles, which predisposed them to neutropenia and diarrhea [24, 25]. The combination of MMC and CPT-11 has been evaluated in solid tumors [26–28]; however, this is the first trial in MBC pts. In terms of efficacy, the median TTP of 4.7 months (95% CI 4.0–5.4 months) is comparable to the results of other trials with single-agent docetaxel, capecitabine, vinorelbine, gemcitabine, CPT-11, pegylated liposomal doxorubicin and MMC with vinblastine in similar MBC pts [16–23].