Long-Term Follow-Up of a Randomized Trial Comparing Concurrent Single Agent Cisplatin, Cisplatin-Based Combination Chemotherapy, or Hydroxyurea During Pelvic Irradiation for Locally Advanced Cervical Cancer: A Gynecologic Oncology Group Study

Roswell Park Cancer Institute, Buffalo, New York, United States
Journal of Clinical Oncology (Impact Factor: 18.43). 07/2007; 25(19):2804-10. DOI: 10.1200/JCO.2006.09.4532
Source: PubMed


We report the long-term survival and toxicity of a randomized phase III study comparing cisplatin alone with cisplatin, flurouracil, and hydroxyurea versus hydroxyurea concurrent with pelvic irradiation for patients with locally advanced cervical cancer with pathologically negative para-aortic nodes.
Comparisons of progression-free (PFS) and overall survival (OS) between treatment arms utilized Kaplan-Meier and log-rank statistics. Relative risk estimates adjusting for prognostic factors were determined using the Cox proportional hazards regression model. Pearson's 2 test was used to assess differences in adverse events.
The analysis included 526 patients. The median follow-up among surviving patients was 106 months. Consistent with the original report, improvement in PFS and OS was evident for both cisplatin-containing arms compared with hydroxyurea (P < .001). Analogous results were seen for stage IIB and for stage III disease (each P < .025). The relative risk of progression of disease or death was 0.57 (95% CI, 0.43 to 0.75) with cisplatin and 0.51 (95% CI, 0.38 to 0.67) with cisplatin-based combination chemotherapy compared with hydroxyurea. Among 518 patients who received radiation, acute (grade 3 or 4) gastrointestinal or urologic toxicities occurred in 66 with cisplatin (19.1%) and 29 with hydroxyurea (16.8%). Delayed radiation toxicity occurred in six patients who received cisplatin (1.7%) and two who received hydroxyurea (1.2%; P = .680).
Cisplatin-based chemotherapy during pelvic radiation therapy improves long-term PFS and OS among locally advanced cervical cancer patients collectively and for stage IIB and III disease, individually. There was no observed increase in late toxicity with cisplatin-based chemoradiotherapy.

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    • "Cervical cancer is a leading cause of mortality in women worldwide [1]. The primary treatment of very early stage disease (IA1-IB1) is surgery and for more advanced disease (larger IB1-IVA) radiotherapy combined with chemotherapy23456. Clinical staging based on physical exam combined with multimodality imaging is of utmost importance as it determines whether a woman is eligible for surgery and also describes the extent of the cancer for women who are not surgical candidates. "
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    ABSTRACT: Cervical cancer is a leading cause of mortality in women worldwide. Staging and management of cervical cancer has for many years been based on clinical exam and basic imaging such as intravenous pyelogram and x-ray. Unfortunately, despite advances in radiotherapy and the inclusion of chemotherapy in the standard plan for locally advanced disease, local control has been unsatisfactory. This situation has changed only recently with the increasing implementation of magnetic resonance image (MRI)-guided brachytherapy. The purpose of this article is therefore to provide an overview of the benefits of MRI in the evaluation and management of cervical cancer for both external beam radiotherapy and brachytherapy and to provide a practical approach if access to MRI is limited.
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    • "However during follow-up period, we had 30 recurrences (58.8%) including 20 patients (39.2%) with local failure, which was higher than results of previously reported investigators (18-24.2%) [4,10,16,17]. Duration of radiotherapy was relatively longer in this study, but this may not be the cause of relatively higher recurrence rate of this study. A meta-analysis of 18 trials from British group could not find any survival difference according to the duration of radiotherapy [8]. "
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    ABSTRACT: To evaluate the clinical efficacy of concurrent chemoradiotherapy (CCRT) using daily low-dose cisplatin for cervical cancer. Fifty-one patients with locally advanced cervical cancer (FIGO stage IB2, bulky IIA, IIB-IVA) who were treated with CCRT as primary therapy at Kurume University Hospital between 2000 and 2007 were retrospectively reviewed. CCRT consisted of 5 mg/m(2)/day of cisplatin 5 days per week, and external beam radiotherapy (EBRT) administrated to whole pelvis to 45-50.6 Gy. High-dose-rate intracavitary brachytherapy was delivered in a single dose of 4-5 Gy at point A, once a week after 20-30 Gy of EBRT. The median follow-up duration was 42 months (range, 5 to 116 months). The overall response rate was 94.1%. Five year overall survival rate was 71.5% and 46.2% in stage I or II, and stage III or IVA, respectively. During follow-up period, 30 recurrences (58.8%) were found, the local failure rate was 39%, and distant failure rate was 35.2%, and both (local and distant) were 15.7%. Hematological toxicities were the most frequent acute toxicities. Grade 3 and 4 neutropenia was observed in 37.3%. Late intestinal toxicities appeared in 7 cases (13.7%), which occurred between 6 and 114 months after treatment. Four cases required bowel surgery. CCRT using daily low-dose cisplatin was tolerable and showed favorable initial response as the primary therapy for locally advanced uterine cervical cancer. But there was no remarkable long-term benefit for patients' survival or local disease control in this study. The incidence of late intestinal toxicity still requires further investigation.
    Full-text · Article · Apr 2013 · Journal of Gynecologic Oncology
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    • "Beginning in 2002, they gradually replaced cisplatin and 5-FU with weekly cisplatin. The reason was weekly cisplatin chemotherapy had less toxicity (Rose et al., 2007). Platinum-based chemotherapy includes cisplatin, carboplatin and nedaplatin. "
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    ABSTRACT: Aims: To evaluate the adverse effect and survival outcome of weekly and triweekly cisplatin with radiotherapy in treatment of cervical cancer. Methods: After an extensive literature search between 1995-2011,we analyzed 7 studies to compare weekly cisplatin and triweekly cisplatin combined radiotherapy. Results: Our analysis established that weekly cisplatin has a lower risk of hematologic toxicity than triweekly cisplatin with concurrent radiotherapy in the treatment of cervical cancer. However, there were no differences in progression free survival and overall survival between weekly cisplatin and triweekly cisplatin (p>0.05). Conclusions: Weekly cisplatin combined with concurrent radiation has lower risk in hematologic toxicity than triweekly cisplatin, but does not improve survival. Triweekly cisplatin treatment has longer intervals and is therefore more convenient. Clinicians and patients can choose either weekly cisplatin or triweekly cisplatin combined radiotherapy for cervical cancer.
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