Concurrent Weekly Nedaplatin, External Beam Radiotherapy and High-Dose-Rate Brachytherapy in Patients with FIGO Stage IIIb Cervical Cancer: A Comparison with a Cohort Treated by Radiotherapy Alone

Objectives: The aim of this study was to evaluate whether nedaplatin-based concurrent chemoradiotherapy (CCRT) using high-dose-rate intracavitary brachytherapy (HDR-ICBT) is superior to radiotherapy (RT) alone in patients with FIGO stage IIIb cervical cancer. Methods: The records of 41 consecutive women treated either with nedaplatin-based CCRT using HDR-ICBT (n = 20) or RT alone (nonrandomized control group, n = 21) for stage IIIb cervical cancer were retrospectively reviewed. The activity and toxicity were compared between the two treatment groups. Progression-free survival (PFS) and overall survival (OS) were the main endpoints. Results: The 5-year overall survival rates in the CCRT and RT groups were 65 and 33.3%, respectively. The median OS of the CCRT and RT groups were 60 and 29 months, respectively. CCRT was significantly superior to RT alone with regard to PFS (p = 0.0015) and OS (p = 0.0364). The frequency of acute grade 3–4 toxicity was significantly higher in the CCRT group than in the RT group. However, no statistically significant difference was observed with regard to severe late toxicity. Conclusions: Nedaplatin-based concurrent chemoradiotherapy was safely performed and significantly improved the prognosis of patients with FIGO stage IIIb cervical cancer. This treatment can be considered as an alternative to cisplatin-based chemoradiotherapy in this patient population.

[1]  T. Enomoto,et al.  The activity of carboplatin and paclitaxel for recurrent cervical cancer after definitive radiotherapy. , 2009, Gynecologic oncology.

[2]  N. Yaegashi,et al.  A phase II multicenter trial of concurrent chemoradiotherapy with weekly nedaplatin in advanced uterine cervical carcinoma: Tohoku Gynecologic Cancer Unit Study. , 2008, Oncology Report.

[3]  Y. Akino,et al.  Patterns of radiotherapy practice for patients with cervical cancer (1999-2001): patterns of care study in Japan. , 2008, International journal of radiation oncology, biology, physics.

[4]  S. Kanazawa,et al.  Phase I study of weekly nedaplatin and concurrent pelvic radiotherapy as adjuvant therapy after radical surgery for cervical cancer , 2007, International Journal of Gynecologic Cancer.

[5]  S. Kalnicki,et al.  Efficacy and toxicity of concomitant cisplatin with external beam pelvic radiotherapy and two high-dose-rate brachytherapy insertions for the treatment of locally advanced cervical cancer. , 2007, Gynecologic oncology.

[6]  K. Matsuo,et al.  Phase II study of radiation therapy combined with weekly nedaplatin in locally advanced uterine cervical carcinoma (LAUCC): Kitasato Gynecologic Radiation Oncology Group (KGROG 0501)--initial analysis. , 2007, European journal of gynaecological oncology.

[7]  Wei-Chun Chang,et al.  Concurrent weekly cisplatin plus external beam radiotherapy and high-dose rate brachytherapy for advanced cervical cancer: a control cohort comparison with radiation alone on treatment outcome and complications. , 2006, International journal of radiation oncology, biology, physics.

[8]  P. Maisonneuve,et al.  Carcinoma of the cervix uteri , 2003, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[9]  J. Dimopoulos,et al.  3D conformal HDR-brachy- and external beam therapy plus simultaneous cisplatin for high-risk cervical cancer: clinical experience with 3 year follow-up. , 2006, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[10]  T. Takayama,et al.  A phase I/II study of nedaplatin and 5-fluorouracil with concurrent radiotherapy in patients with esophageal cancer , 2006, Cancer Chemotherapy and Pharmacology.

[11]  Y. Kawai,et al.  Relationship between cisplatin or nedaplatin-induced nephrotoxicity and renal accumulation. , 2005, Biological & pharmaceutical bulletin.

[12]  T. Uehara,et al.  Nephrotoxicity of a novel antineoplastic platinum complex, nedaplatin: a comparative study with cisplatin in rats , 2005, Archives of Toxicology.

[13]  S. H. Cheng,et al.  Extended-field radiotherapy and high-dose-rate brachytherapy with concurrent and adjuvant cisplatin-based chemotherapy for locally advanced cervical cancer: a phase I/II study. , 2005, Gynecologic oncology.

[14]  K. Ogawa,et al.  Concurrent chemoradiotherapy using high-dose-rate intracavitary brachytherapy for uterine cervical cancer. , 2005, Gynecologic oncology.

[15]  C. Khorprasert,et al.  Phase III randomized trial comparing LDR and HDR brachytherapy in treatment of cervical carcinoma. , 2004, International journal of radiation oncology, biology, physics.

[16]  Mitchell Morris,et al.  Pelvic irradiation with concurrent chemotherapy versus pelvic and para-aortic irradiation for high-risk cervical cancer: an update of radiation therapy oncology group trial (RTOG) 90-01. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  M. Hareyama,et al.  High-dose-rate versus low-dose-rate intracavitary therapy for carcinoma of the uterine cervix: a randomized trial , 2002 .

[18]  L Souhami,et al.  Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  Paul Symonds,et al.  Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis , 2001, The Lancet.

[20]  M. Hasegawa,et al.  Induction of p53-dependent apoptosis in vivo by nedaplatin and ionizing radiation. , 2000, Oncology reports.

[21]  B N Bundy,et al.  Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  P J Eifel,et al.  Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. , 1999, The New England journal of medicine.

[23]  B N Bundy,et al.  Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. , 1999, The New England journal of medicine.

[24]  B N Bundy,et al.  Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. , 1999, The New England journal of medicine.

[25]  D. Alberts,et al.  In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human cervical cancers. , 1998, Gynecologic oncology.

[26]  T. Pajak,et al.  Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) , 1995, International journal of radiation oncology, biology, physics.

[27]  H. Jones,et al.  Prognostic significance of ureteral obstruction in primary cervical cancer , 1994, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[28]  T. Kozuka,et al.  High‐dose rate and low‐dose rate intracavitary therapy for carcinoma of the uterine cervix. Final results of osaka university hospital , 1993, Cancer.

[29]  Y. Inuyama,et al.  [A late phase II clinical study of cis-diammine glycolato platinum, 254-S, for head and neck cancers]. , 1992, Gan to kagaku ryoho. Cancer & chemotherapy.

[30]  M. Yakushiji,et al.  [Phase II study of 254-S (cis-diammine glycolato platinum) for gynecological cancer]. , 1992, Gan to kagaku ryoho. Cancer & chemotherapy.

[31]  P. Grigsby,et al.  The effect of volume of disease in patients with carcinoma of the uterine cervix. , 1991, International journal of radiation oncology, biology, physics.

[32]  K. Eguchi,et al.  Phase I study and pharmacological analysis of cis-diammine(glycolato)platinum (254-S; NSC 375101D) administered by 5-day continuous intravenous infusion. , 1991, Cancer research.

[33]  M. Gemba,et al.  Nephrotoxicity of a new platinum compound, 254-S, evaluated with rat kidney cortical slices. , 1990, Toxicology letters.

[34]  K. Eguchi,et al.  Phase II study of (glycolate-O,O′) diammineplatinum(II), a novel platinum complex, in the treatment of non-small-cell lung cancer , 2008, Cancer Chemotherapy and Pharmacology.

[35]  N. Umesaki,et al.  Radiation reduces carboplatin sensitivity and enhances nedaplatin sensitivity in cervical squamous cell carcinoma in vitro. , 2007, European journal of gynaecological oncology.

[36]  N. Yaegashi,et al.  Phase I trial of concurrent chemoradiation with weekly nedaplatin in patients with squamous cell carcinoma of the uterine cervix. , 2007, Gynecologic oncology.

[37]  K. Eguchi,et al.  Prediction of the antitumor activity of new platinum analogs based on their ex vivo pharmacodynamics as determined by bioassay , 2004, Cancer Chemotherapy and Pharmacology.

[38]  M. Hareyama,et al.  High‐dose‐rate versus low‐dose‐rate intracavitary therapy for carcinoma of the uterine cervix , 2002, Cancer.

[39]  K. Blank,et al.  Concurrent Cisplatin-Based Radiotherapy and Chemotherapy for Locally Advanced Cervical Cancer , 1999 .

[40]  D. Alberts,et al.  In vitro phase II comparison of the cytotoxicity of a novel platinum analog, nedaplatin (254-S), with that of cisplatin and carboplatin against fresh, human ovarian cancers , 1997, Cancer Chemotherapy and Pharmacology.

[41]  Y. Inuyama,et al.  [An early phase II clinical study of cis-diammine glycolato platinum, 254-S, for head and neck cancers]. , 1992, Gan to kagaku ryoho. Cancer & chemotherapy.

[42]  R. Gori.  [Carcinoma of the cervix uteri]. , 1970, Prensa medica argentina.

[43]  E S Hafez,et al.  Uterine cervix. , 1969, Science.

[44]  H. Wespi.  [Cervical carcinoma]. , 1953, Der Krebsarzt.