Cervical non-squamous carcinoma: an effective combination chemotherapy of taxane, anthracycline and platinum for advanced or recurrent cases

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Abstract

Objective

An effective salvage chemotherapy for advanced and recurrent non-squamous carcinoma of the uterine cervix has not yet been established. The aim of the present study was to analyze the safety and efficacy of a combination chemotherapy for this disease using taxane, anthracycline, and platinum.

Study design

This was a retrospective analysis of advanced and recurrent non-squamous cervical cancers treated at the Osaka University Hospital and the Osaka Medical Center for Cancer and Cardiovascular Diseases during a 10 year study period from 2000 to 2009. Single agent chemotherapies and combination chemotherapies for advanced and recurrent cervical cancer cases of non-squamous histology which were reported in the English literature were also reviewed.

Results

Salvage chemotherapy, using taxane, anthracycline and platinum, was performed for 5 advanced and 14 recurrent cases. Prior to the salvage chemotherapy, 15 (79%) of the 19 patients had already received either radiation or chemotherapy. A complete or partial tumor response was achieved in 8 (42%) of the 19 cases. The response rate for recurrent disease in a previously irradiated field was 40%. The median progression-free survival (PFS) and overall survival (OS) were 8 months (1–108) and 13 months (5–108), respectively. Grade 4 and febrile grade 3 neutropenia was observed in 6 cases (32%), but there was no case in which salvage chemotherapy had to be cancelled due to toxicity. According to previous reports, the cumulative response rate of combination chemotherapy (35%) was significantly higher than that of single agent chemotherapy (17%) (p < 0.001). OS tended to be longer in the combination chemotherapy cases (8.7 months to 18 months) than that of single agent chemotherapy cases (7.3+ months to 9.1+ months).

Conclusion

Combination chemotherapy of taxane, anthracycline, and platinum was found to have a survival benefit for advanced and recurrent cervical cancer patients of non-squamous carcinoma histology, with a tolerable toxicity.

Introduction

Cervical cancer is the second most common cancer of women in the world, and nearly 4000 patients die of the disease annually in the United States [1]. Approximately 85–90% of these cervical cancers are squamous cell carcinomas and most of the remaining 10–15% are adenocarcinomas [2]. The incidence of adenocarcinoma, which has been demonstrated to be an independent prognostic factor for cervical cancer [3], [4], has been on the rise, especially in younger women [5].

Cervical cancer is usually treated by surgery, radiation or chemoradiotherapy. It is estimated that approximately 35% of patients with cervical cancer will have recurrent or persistent disease after their initial treatment. The prognosis for advanced or recurrent cervical carcinoma is poor, with a 1-year survival rate between 10% and 15% [2]. In a fraction of these cases, the disease is well treated by radical surgery or radiation, but in most cases salvage chemotherapy must be performed. Recurrent or advanced squamous cell carcinoma was demonstrated to exhibit a better response to combination chemotherapy of cisplatin and paclitaxel than to single-agent chemotherapy of cisplatin in a randomized study [6]. Combination chemotherapy using paclitaxel and carboplatin was also shown to be more effective for advanced or recurrent cervical cancer cases, most of which were squamous cell carcinoma [7].

Recently, Takekida et al. showed that combination chemotherapy of docetaxel and carboplatin was effective in a case of recurrent adenocarcinoma of the uterine cervix and also effective as a neoadjuvant chemotherapy (NAC) in 20 (69%) of 29 other non-squamous carcinoma cases [8].

To date, most large studies of salvage chemotherapy for advanced or recurrent cervical cancer have targeted the more common squamous cell carcinoma [6], whereas salvage chemotherapy for advanced and recurrent non-squamous carcinoma of the uterine cervix has not yet been established. In the present study, we performed a retrospective analysis of the efficacy and adverse effect of a salvage chemotherapy that uses taxane, anthracycline, and platinum for advanced and recurrent non-squamous carcinoma of the uterine cervix, and a literature review of salvage chemotherapy for those cases.

Section snippets

Materials and methods

Advanced or recurrent cases of non-squamous carcinoma of the uterine cervix, in which salvage chemotherapy using taxane, anthracycline, and platinum was performed at the Osaka University Hospital and the Osaka Medical Center for Cancer and Cardiovascular Diseases during the period of 2000–2009 (10-year period), were retrospectively analyzed. Locally advanced, bulky tumors were excluded from the present analysis, but persistent tumors after initial therapy, and primary tumors with distant

Salvage chemotherapy using taxane, anthracycline and platinum

Salvage chemotherapy using taxane, anthracycline, and platinum was preformed in 19 advanced or recurrent cases of non-squamous carcinoma of the uterine cervix at the Osaka Medical Center for Cancer and Cardiovascular Diseases and the Osaka University Hospital during the period 2000–2009. TPP (150 mg/m2 for paclitaxel, 40 mg/m2 for pirarubicin and 50 mg/m2 for cisplatin), TEC (150 mg/m2 for paclitaxel, 50 mg/m2 for epirubicin and AUC 4 for carboplatin), and TPN (150 mg/m2 for paclitaxel, 40 mg/m2 for

Comment

The incidence of cervical adenocarcinoma has been increasing, especially in younger women [5]. Adenocarcinoma was demonstrated to be an independent prognostic factor [3], [4]. In a randomized study, recurrent or advanced squamous cell carcinoma was demonstrated to exhibit a better response to combination chemotherapy of cisplatin and paclitaxel than to a single agent chemotherapy of cisplatin [6]. Bernett et al. demonstrated that the combination chemotherapy of gemcitabine and cisplatin was

Authors’ contributions

Toshihiro Kimura and Takashi Miyatake: Data collection and analysis.

Yutaka Ueda: Study design, analysis of data and preparation of the manuscript.

Yukinobu Ohta: Data analysis.

Shoji Kamiura, Takayuki Enomoto, Tadashi Kimura: Data analysis and approval of the study.

Conflict of interest statement

The authors have no conflicts of interest to declare.

Funding

None.

Ethical approval

All patients provided written informed consent before their treatments commenced. This study was approved by the Ethics Committee of Osaka University Hospital (#10302, March 11, 2011).

Acknowledgement

We would like to thank Dr. G.S. Buzard, CDCP, for his constructive editing of our manuscript.

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    • A Phase II Study of S-1 plus Oxaliplatin for Patients with Recurrent Non-Squamous Cell Carcinoma of the Uterine Cervix (Tohoku Gynecologic Cancer Unit: TGCU206 Study)

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    1

    These two authors contributed equally to this work.

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