Japanese Journal of Clinical Oncology Advance Access originally published online on January 4, 2007
Japanese Journal of Clinical Oncology 2007 37(1):70-72; doi:10.1093/jjco/hyl153
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© 2007 Foundation for Promotion of Cancer Research
Phase II Study of Radiation Therapy Combined with Weekly Nedaplatin in Locally Advanced Uterine Cervical Carcinoma: Kitasato Gynecologic Radiation Oncology Group (KGROG 0501)
1 Department of Radiology, Kitasato University School of Medicine, Sagamihara, Kanagawa
2 Department of Obstetrics and Gynecology, Kitasato University School of Medicine, Sagamihara, Kanagawa
3 Division of Pharmacology, Kitasato University Hospital, Sagamihara, Kanagawa, Japan
For reprints and all correspondence: Yuzuru Niibe, Department of Radiology, Kitasto University School of Medicine, 1-15-1, Kitasato, Sagamihara, Kanagawa 225-8555, Japan. E-mail: joe-n{at}hkg.odn.ne.jp
Received December 20, 2005; accepted April 11, 2006
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Abstract |
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 TOP Abstract INTRODUCTIONPROTOCOL SUMMARY FOR STUDY...ENDPOINTSELIGIBILITY CRITERIAEXCLUSION CRITERIATREATMENT METHODSConflict of interest statementReferences |
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In order to evaluate the safety and efficacy of chemoradiotherapy using nedaplatin for locally advanced uterine cervical carcinoma in Japanese patients, we have started a single-institute phase II trial. Eligibility criteria include: (i) pathologically proven squamous cell carcinoma or adenocarcinoma, (ii) clinical FIGO stage Ib, IIa, or IIb with bulky tumor (> 40 mm) or pelvic lymph node swelling, or (iii) clinical FIGO stage IIIa, IIIb and IVa, (iv) no para-aortic lymph node swelling. A combination of external beam radiation and high dose rate intracavitary irradiation is given. Nedaplatin (30 mg/m2) is intravenously infused on a weekly basis for five times. The primary endpoint is 3-year overall survival, and the secondary endpoints are tumor response, 2-year overall survival, 3-year progression-free survival, acute adverse events, protocol treatment compliance, and late adverse events. We plan to recruit 45 patients within 3 years.
Key Words: chemoradiotherapy • locally advanced uterine cervical carcinoma • nedaplatin • phase II study
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INTRODUCTION |
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TOPAbstractINTRODUCTIONPROTOCOL SUMMARY FOR STUDY...ENDPOINTSELIGIBILITY CRITERIAEXCLUSION CRITERIATREATMENT METHODSConflict of interest statementReferences |
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Concurrent chemoradiotherapy for locally advanced uterine cervical carcinoma (LAUCC) has been demonstrated to be superior to radiation therapy alone in five major clinical trials in the USA (1–5), and the National Cancer Institute made a strong recommendation of concurrent chemoradiotherapy for the disease. In Japan, concurrent chemoradiotherapy including platinum agents has also been widely used for LAUCC. However, there exists a major difference in radiation therapy between the USA and Japan. In the USA, the external beam radiation therapy is first given and the low dose rate intracavitary irradiation follows. In Japan, the high dose rate intracavitary irradiation is performed concomitantly with external radiation therapy using central shielding. This shortens overall treatment time and enables more intense treatment without increasing morbidity due to central shielding.
Cisplatin is the standard agent for this chemoradiotherapy in Japan. Weekly intravenous administration of cisplatin usually requires heavy hydration and hospitalization, which may reduce the compliance of this treatment. Nedaplatin, another platinum agent, has been shown to have similar anti-tumor activity to cisplatin with lower renal toxicity, and can be administered in the out-patient setting. A phase I study of concurrent nedaplatin and radiation for LAUCC was already completed (6).
In this phase II trial KGROG 0501, we evaluate the safety and efficacy of concurrent nedaplatin administration and combination radiotherapy consisting of external beam and concomitant high dose rate intracavitary irradiation using central shielding.
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PROTOCOL SUMMARY FOR STUDY KGROG0501 |
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TOPAbstractINTRODUCTIONPROTOCOL SUMMARY FOR STUDY...ENDPOINTSELIGIBILITY CRITERIAEXCLUSION CRITERIATREATMENT METHODSConflict of interest statementReferences |
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Purpose
The aim is to evaluate the efficacy and safety of chemoradiotherapy for LAUCC in a Japanese population.
Study Setting
This study is a single-institute, single-arm phase II trial. The protocol was approved by the ethics and protocol review committee of Kitasato University.
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ENDPOINTS |
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TOPAbstractINTRODUCTIONPROTOCOL SUMMARY FOR STUDY...ENDPOINTSELIGIBILITY CRITERIAEXCLUSION CRITERIATREATMENT METHODSConflict of interest statementReferences |
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The primary endpoint is 3-year overall survival, and the secondary endpoints are tumor response, 2-year overall survival, 3-year progression-free survival, acute adverse events, protocol treatment compliance and late adverse events.
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ELIGIBILITY CRITERIA |
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TOPAbstractINTRODUCTIONPROTOCOL SUMMARY FOR STUDY...ENDPOINTSELIGIBILITY CRITERIAEXCLUSION CRITERIATREATMENT METHODSConflict of interest statementReferences |
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- Pathologically proven squamous cell carcinoma or adenocarcinoma;
- No para-aortic lymph node swelling (
10 mm) by abdominal computed tomography;
- Clinical FIGO stage Ib, IIa, IIb with bulky tumor ( 40 mm assessed by pelvic magnetic resonance imaging) or pelvic lymph node swelling ( 10 mm assessed by pelvic computed tomography);
- Clinical FIGO stage IIIa, IIIb and IVa;
- Age: 20–75 years;
- Perfomance status (Eastern Cooperative Oncology Group): 0–2;
- No prior radiation therapy for abdomen;
- Adequate function of bone marrow, kidney and liver (white blood cell count 2500 mm3, neutrophil 1000 mm3, hemoglobin 8.0 g/dl, platelet count 75 000 mm3, creatinine
2.0 mg/dl, 24 h-Ccr 60 ml/min, GOT and GPT 2 times of the upper limit of normal at our institution, T.Bil 2 times of the upper limit of normal at our institution); and
- Written informed consent.
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EXCLUSION CRITERIA |
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TOPAbstractINTRODUCTIONPROTOCOL SUMMARY FOR STUDY...ENDPOINTSELIGIBILITY CRITERIAEXCLUSION CRITERIATREATMENT METHODSConflict of interest statementReferences |
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- Active other cancers except carcinoma in situ or controlled for more than 2 years;
- Use of long-term and continuous steroid;
- Serious complications (heart disease within 3 months, chronic heart failure, neurovascular disease within 3 months, uncontrolled infectious disease); and
- Judged to be ineligible for this protocol by the attending physicians.
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TREATMENT METHODS |
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TOPAbstractINTRODUCTIONPROTOCOL SUMMARY FOR STUDY...ENDPOINTSELIGIBILITY CRITERIAEXCLUSION CRITERIATREATMENT METHODSConflict of interest statementReferences |
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Radiation Therapy
External Beam Radiation Therapy
External beam radiation therapy protocol using 10 MV X-ray is as follows. The fractionation will be 1.8–2.0 Gy, five fractions per week, totaling 30–32 Gy using the entire pelvic irradiation field without central shielding, followed by 2 Gy per fraction, five fractions per week totaling 20 Gy using the entire pelvic field with central shielding. Thus, the total dose will be 50–52 Gy.
Intracavitary Irradiation
Intracavitary irradiation, of which the fraction size is 5–6 Gy to point A, will be given once a week for a total of four to six times (in case of 6 Gy fraction size, maximun four times). The total dose to point A will be 20–30 Gy.
Chemotherapy
Nedaplatin (30 mg/m2) is dissolved in 500 ml of 0.9% sodium chloride and infused intravenously over 3 h. The first infusion is performed at the starting day of the external beam radiation therapy.
The regimen is repeated weekly for a total of five times (at least three courses should be given).
Follow-Up
All eligible subjects will be included in the assessment of efficacy and safety. Non-evaluable subjects will only be added into the efficacy assessment data set as not evaluable (NE). The following data will be recorded (i) dates of treatment start (external beam radiation therapy, intracavitary irradiation, and infusion of nedaplatin), (ii) maximum tumor response and the date of achieving the maximum tumor response, (iii) final date of assessing survival, (iv) date of death, (v) final date of assessing time to progression and (vi) date of progression.
Study Design and Statistical Methods
The expected 3-year overall survival rate is 40% and the threshold value is defined as 20%. The sample size was calculated as 45 (
= 0.05 and ß = 0.1, non-compliance 10%). The duration of registration will be 3 years, starting in June 2005 and ending in May 2008. All patients will be followed up for 3 years.
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Conflict of interest statement |
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TOPAbstractINTRODUCTIONPROTOCOL SUMMARY FOR STUDY...ENDPOINTSELIGIBILITY CRITERIAEXCLUSION CRITERIATREATMENT METHODSConflict of interest statementReferences |
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None declared.
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Acknowledgments |
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This study was supported in part by a grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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References |
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TOPAbstractINTRODUCTIONPROTOCOL SUMMARY FOR STUDY...ENDPOINTSELIGIBILITY CRITERIAEXCLUSION CRITERIATREATMENT METHODSConflict of interest statementReferences |
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1 Keys HM, Bundy BN, Stehman FB, Munderspach LI, Chafe WE, Suggs CL 3rd, et al. (1999) Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for buky stage IB cervical carcinoma. N Eng J Med 40 1154–61.
2 Whitney CW, Sause W, Bundy BN, Malfetano JH, Hanningan EV, Fowler WC Jr, et al. (1999) Randomized comparison of fluorouracil plus cisplatin versus hydroxyRiurea 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. J Clin Oncol 17 1339–48.
3 Morris M, Eifel PJ, Lu J, Grigsby PW, Levenbach C, Stevens RE, et al. (1999) Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Eng J Med 340 1137–43.
4 Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS, et al. (2000) Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 18 1606–13.
5 Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, et al. (1999) Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Eng J Med 340 1144–53.
6 Idei T, Sakamoto H, Nakajima Y, Hiraiwa Y, Takami N, Chishima F, et al. (2003) Concurrent weekly nedaplatin-based radiotherapy for high risk, recurrent and advanced cervical cancer. Gan To Kagaku Ryoho 30 505–9.[Medline]
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