A Phase II Trial with Cisplatin-Paclitaxel Cytotoxic Treatment and Concurrent External and Endocavitary Radiation Therapy in Locally Advanced or Recurrent Cervical Cancer

Abstract

Background: Five randomized studies have demonstrated a beneficial effect of adding cisplatin-based chemotherapy to radiation therapy in the treatment of cervical carcinoma. In the present phase II study, we evaluated the response and toxicity of ciplatin-Taxol chemotherapy combined with concomitant radiotherapy in patients with locally advanced cervical carcinoma (LACC) and locally recurrent cervical carcinoma (LRCC). Patients and Methods: In 2000, this phase II study was initiated with a chemotherapy regimen of cisplatin (75 mg/m²) and Taxol (175 mg/m²) every 21 days, for four cycles, concomitant with external radiotherapy and high-dose-rate brachytherapy. Pelvic radiotherapy was started 2 weeks after the first chemotherapy cycle, while the first brachytherapy insertion was carried out during the fourth chemotherapy cycle. SCC marker was determined before treatment and after every chemotherapy cycle. Results: All of the 27 patients treated achieved a complete clinical response. Two patients with LACC experienced distant recurrence 22 and 24 months after complete response, respectively, and 1 patient with LRCC had local progression 6 months after the end of radiotherapy. Although generally tolerable, neutropenia grade 3–4 in 4 patients and anemia grade 3 in 2 patients were observed, and 1 patient experienced grade 2 neurotoxicity; toxicity due to radiotherapy was moderate. Conclusions: Concomitant cisplatin-Taxol chemoradiotherapy seems to be well tolerated, and results, even in this small series, are encouraging.

Concurrent chemoradiotherapy with paclitaxel and cisplatin for patients of locally advanced cervical squamous cell carcinoma: A single-arm phase II clinical study

“…The median RT time in our study was 62 d, similar to the 63-d median reported by Miglietta et al [8]. Adverse effects in our trial were generally tolerable and mild.…”

“…Due to additional cycle of neoadjuvant chemotherapy before CCRT, Miglieta et al observed full complete clinical response rate and maintained local control [8]. It was assumed that high dose of PTX (175 mg/m 2 every 3 weeks for four cycles) in chemotherapy regimen would contribute to favourable tumor regression in that study.…”

“…PTX, a taxane compound, has been shown to have high efficacy against solid tumors, especially epithelial ovarian cancer, lung, and breast cancer tumors [8]. PTX cytotoxicity of human cervical cancer cells has been shown to involve inhibition the Raf-1 kinase activity.…”

Comparison of concurrent chemoradiotherapy with cisplatin plus 5-fluorouracil versus cisplatin plus paclitaxel in patients with locally advanced cervical carcinoma

“…every 3 weeks for four cycles, 25% and 16% patients display grade 3 or 4 leukopenia and grade 3 or 4 neutropenia, respectively. 12 The reason why our study shows a higher frequency of leukopenia and neutropenia might be explained by a dosage effect, i.e., 4 cycles of paclitaxel (135 mg/m 2 ) combined with cisplatin and radiation in this study might be too much for Asian women. This is in accordance with a Japanese study which reported that the grades of hematological toxicity are significantly greater in weekly cisplatin treatment groups at 40 mg/m 2 (conventional dose in chemoradiation) than at 30 mg/m 2 .…”

“…10 Recently, several studies which used cisplatin plus paclitaxel with concurrent radiation have been reported. 9,[11][12][13] These were phase I and/or II studies which focused on evaluating toxicities and response rates in a limited number of enrolled patients. These studies have demonstrated that cisplatin plus paclitaxel concurrently used with radiation show encouraging response rate and good tolerability.…”