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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    • "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.
    Journal of Gynecologic Oncology 04/2013; 24(2):108-13. DOI:10.3802/jgo.2013.24.2.108 · 2.49 Impact Factor
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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.
    Asian Pacific journal of cancer prevention: APJCP 09/2012; 13(9):4301-4. DOI:10.7314/APJCP.2012.13.9.4301 · 2.51 Impact Factor
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    • "Several studies demonstrate that concurrent chemoradiotherapy is better than chemotherapy alone preoperatively (Eifel et al., 2004; Pearcey et al., 2007; Rose et al., 2007; Stehman et al., 2007), which is also implied in our study. Compared to neoadjuvant chemotherapy, the pelvic recurrence within two years was statistically significantly lower in the concurrent chemoradiotherapy group, while the 5-year survival was not statistically significantly higher than the other groups, which agrees well with the findings that neoadjuvant chemotherapy achieves high short-term response but does not affect long-term survival much (Eddy et al., 2007). "
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    ABSTRACT: To compare the clinical efficacy of concurrent chemoradiotherapy, neoadjuvant chemotherapy, and intracavity brachytherapy in comprehensive treatment for young patients with stage Ib2 cervical cancer. One hundred and twelve young patients with stage Ib2 cervical cancer were enrolled retrospectively in our hospital from January 2003 to June 2005. They were categorized into three groups according to preoperative regimens, including the concurrent chemoradiotherapy group (Group 1, n=38), the neoadjuvant chemotherapy (Group 2, n=49), and the intracavity brachytherapy group (Group 3, n=25). Radical hysterectomy was performed following these regimens. Chemotherapy and radiotherapy were given according to pelvic lymph node metastasis, deep cervical stromal invasion, intravascular cancer emboli, histological grading, vaginal stump and positive surgical margin. The cancer disappearance and superficial muscle invasion rates were statistically significantly better in the concurrent chemoradiotherapy group than in the other two groups (P<0.01). No statistically significant difference was noted in the deep muscle invasion rate, surgical time and intraoperative blood loss among three groups, but significantly more postoperative complications occurred in the concurrent chemoradiotherapy group. The 2-year pelvic recurrence was statistically significantly lower in the concurrent chemoradiotherapy group compared to other two groups, while the 5-year survival was higher. Concurrent chemoradiotherapy is efficacious for young patients with stage Ib2 cervical cancer.
    Asian Pacific journal of cancer prevention: APJCP 04/2012; 13(4):1487-9. DOI:10.7314/APJCP.2012.13.4.1487 · 2.51 Impact Factor
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