Stage IIB-IIIB Cervical Cancer Research Articles

Intensity-modulated radiation therapy for advanced cervical cancer: A comparison of dosimetric and clinical outcomes with conventional radiotherapy

ObjectiveThe aim of this study is to evaluate the dosimetry, efficacy and toxicity of reduced field intensity-modulated radiation therapy (RF-IMRT) for patients with advanced cervical cancer. MethodsFrom August 2005 to August 2010, 60 patients with stage IIB–IIIB cervical cancer underwent reduced field IMRT (RF-IMRT group) and 62 patients treated with conventional radiotherapy (c-RT group) were enrolled. The RF-IMRT plans were as follows: whole pelvic IMRT plan was performed to deliver a dose of 30Gy firstly, then the irradiated volume was reduced to lymphatic drainage region as well as paracervix and parametrium for an additional 30Gy boost. Intracavitary brachytherapy and concurrent chemotherapy were performed during external irradiation. The tumor coverage and normal tissue avoidance were evaluated. Treatment response, toxicities and survival were assessed. ResultsThe mean dose delivered to the planning target volume was significantly higher in RF-IMRT group than in c-RT group (61.5 vs. 50.8Gy, P=0.046). IMRT plans yielded better dose conformity to the target and better sparing of the rectal, bladder and small intestine. The RF-IMRT patients experienced significantly lower acute and chronic toxicities with comparable short-term effects than did those treated with conventional RT (CR: 87.7% vs. 88.3%, P=0.496; PR: 7.0% vs. 6.7%, P=0.440). No significant differences were found between treatment groups for 1year, 3year, and 5year overall survival (OS) levels, although the latter approached statistical significance in favor of IMRT, while a significantly higher progression-free survival (PFS; P=0.031) was seen for IMRT. ConclusionsRF-IMRT yields improved dose distributions, with lower toxicities, while providing comparable clinical outcomes. The increased PFS may be an advantage.

Toxicities and response of concurrent chemoradiotherapy for stage IIB-IIIB cervical cancer.

e15549 Background: Cervical cancer is the most common cancer in women in Vietnam. Concurrent chemoradiotherapy (CCRT) has been proved survival benefit and emerged as the standard treatment of locally advanced cervical cancer. However, it significantly increases early toxicities. This study evaluated the acute toxicities and responses of CCRT in treatment of stage IIB-IIIB cervical cancer in Vietnam. Methods: From November 2006 to December 2007, 60 patients with stage IIB-IIIB cervical cancer were treated by CCRT. EBRT consisted of 40 Gy/20 fractions, followed by 10 Gy boost to the parametrium and intracavitary HDR brachytherapy 7 Gy to point A/fraction/week in 3 fractions. Chemotherapy with cisplatin 40 mg/m2/weekly for 6 cycles started by the first day of EBRT. Results: All the patients completed treatment protocol. Grade 3-4 leukopenia, neutropenia, and thrombocytopenia were 40%, 33.3%, 8.3% respectively. 19 cases (31.7%) had renal toxicity (grade 1: 16 cases, grade 2: 2 cases, and grade 3: 1 case). Grade 3-4 toxicities increased sharply after the fourth cycle of chemotherapy. Mean overall treatment time is 72 days. 15 patients (25%) had to delay treatment mainly due to hematologic toxicity (10/15 cases). The overall response rate was 96.7% (complete response: 81.7%; partial response: 15%). Conclusions: CCRT is relatively high hematologic toxicities and high response rate. This study pointed out the relationship between the risk of toxicities and number of chemotherapy cycles. CCRT with 5 cycles of chemotherapy would decrease toxicities and overall treatment time. No significant financial relationships to disclose.

Neoadjuvant intraarterial chemotherapy for stage IIB–IIIB cervical cancer in Japanese women

Chemoradiotherapy is currently the main treatment for locally advanced cervical cancer, but neoadjuvant intraarterial chemotherapy (IA-NAC) has been reported to achieve favorable results. This study investigated the efficacy of several different IA-NAC regimens. The subjects were 55 patients with stage IIB-IIIB cervical cancer who received IA-NAC between January 1991 and April 2006. IA-NAC was administered for a total of 1-3 courses at 3-week intervals, with three different regimens being employed in chronological order. The response rate achieved with IA-NAC was 90.2% for squamous cell carcinoma, 60% for adenosquamous carcinoma and 42.9% for adenocarcinoma. Surgery was performed after IA-NAC in 36 patients, and radiotherapy alone was performed in 19 patients. The 5-year survival rate was 72.9% for patients with squamous cell carcinoma and 50% for those with adenocarcinoma or adenosquamous carcinoma. PAMF therapy (cisplatin, epirubicin, mitomycin-C and 5-fluorouracil) achieved a response rate of ≥90% for squamous cell carcinoma, as did CDDP + THP therapy (cisplatin plus pirarubicin), while PACF therapy (cisplatin, epirubicin, cyclophosphamide and 5-flurouracil) achieved a better response rate for adenosquamous carcinoma and adenocarcinoma. Grade 3 or 4 hematological toxicity was significantly more common with PAMF therapy. In conclusion, IA-NAC improved the survival of patients with squamous cell carcinoma. CDDP + THP therapy achieved a high response rate with little hematologic toxicity. PACF therapy achieved a significantly higher response rate in patients with adenosquamous carcinoma or adenocarcinoma. Therefore, IA-NAC may be a therapeutic option for locally advanced cervical cancer, particularly using the above-mentioned regimens.

Capecitabine-Based Chemoradiotherapy with Adjuvant Capecitabine for Locally Advanced Squamous Carcinoma of the Uterine Cervix: Phase II Results

Cisplatin-based chemoradiotherapy is the standard treatment for locally advanced cervical cancer but causes considerable toxicity. Capecitabine and radiotherapy show preclinical synergy and clinical activity. The activity, tolerability, and oral administration of capecitabine make it an attractive adjunctive therapy. In this phase II study, patients with untreated International Federation of Gynecology and Obstetrics stage IIB-IIIB cervical cancer received capecitabine, 825 mg/m(2) twice daily (Monday-Friday), during radiation (45 Gy per 25 fractions external-beam radiotherapy and 26 Gy high-dose rate brachytherapy to point A, maximum 8 weeks), followed by six cycles of capecitabine, 1,000 mg/m(2) twice daily (days 1-14 every 21 days). The overall response rate in 60 patients was 88% (95% confidence interval [CI], 77.4%-95.2%), including complete responses (CRs) in 80% of patients. The 1-year progression-free and overall survival rates were 86% (95% CI, 77%-95%) and 95% (95% CI, 89%-100%), respectively. At 23 months, 76% of patients were progression free (95% CI, 65%-88%) and CR was maintained in 90% (95% CI, 81%-99%) of the 48 patients achieving a CR. There were three grade 3 or 4 treatment-related events: reversible grade 4 hypokalemia, grade 3 diarrhea, and grade 3 hand-foot syndrome. Capecitabine-based chemoradiotherapy with adjuvant capecitabine is a well-tolerated option with an early signal of efficacy meriting further evaluation.

Analysis of curative effect for concurrent chemoradiotherapy versus neoadjuvant chemotherapy for stage IIB-IIIB cervical cancer.

Objective To observe the effect and side effects of concurrent chemoradiotherapy for stage ⅡB～ⅢB cervical cancer. Methods 126 patients with stage ⅡB～ⅢB cervical cancer were randomly allocated into 2 groups. Concurrent chemoradiotherapy group: radiotherapy carried out same as the neoadjuvant chemotherapy group, i.e.firstly with cisplatin 20 mg iv d1-5, 5-Fu 750 mg iv d1-5, repeated every 28 days, total 4 cycle; the neoadjuvant chemotherapy group i.e.firstly with cisplatin 20 mg iv d1-5, 5-Fu 750 mg iv d1-5, repeated every 28 days, total 2 cycle, after chemotherapy received routine radiotherapy 2 Gy per day, 5 times a week to a total dose of 30 Gy with 192Ir brachytherapy, 7 Gy per week. When total dose reached 46 Gy, the middle field was shielded by plumbum, then continuous radiotherapy, total dose reach A point 65-70 Gy, B point 50-56 Gy. Results All patients were followed-up for more than five years. The follow-up rate was 94.4 %. In concurrent chemoradiotherapy group the 3 year survival rate and the 5 year survival rate were 82.8 %, 65.6 %, In neoadjuvant chemotherapy group the 3 year survival rate and the 5 year survival rate were 67.7 %, 46.8 %. There was a significant difference in two groups (X2=3.86, P＜0.05; X2=5.01, P＜0.05), no significant difference in toxicity-side effect. Conclusion Concurrent chemoradiotherapy for advanced cervical cancer can significantly improve the 3-year and 5-year survival rate and has little increase in toxicity-side effect. Key words: Uterine cervical neoplasms; Chemotherapy, adjuvant; Drug therapy, combination

0491: Nadroparine Activated Fibrinolysis and Renal Function in Patient with Stage Iib-Iiib Cervical Cancer Treated with Radiochemotherapy

0491: Nadroparine Activated Fibrinolysis and Renal Function in Patient with Stage Iib-Iiib Cervical Cancer Treated with Radiochemotherapy

A randomized phase III trial of concurrent chemoradiotherapy in locally advanced cervical cancer: Preliminary results

Concurrent chemoradiation is the standard treatment for locally advanced cervical cancer. This study was a preliminary result of a randomized two arms, prospective, open-label phase III trial comparing the activity and safety of the concurrent chemoradiation of Tegafur-Uracil and carboplatin or carboplatin alone in locally advanced cervical cancer. The stage IIB-IIIB cervical cancer patients were randomized to have Tegafur-Uracil 225 mg/m(2)/day orally, 5 days a week and carboplatin 100 mg/m(2) IV over 30-60 min, weekly on day 1 concurrent with standard radiotherapy (Group A) or carboplatin alone concurrent with standard radiotherapy (Group B). Four hundred and sixty-nine patients were randomized to Group A (n=234) or Group B (n=235). The tumor response at 3-month follow-up time showed no significant difference. The only prognostic factor to improve the complete response rate was the hemoglobin level. The patients in Group A, who had Hb <10 gm/dL had the relatively better change to complete response of 1.48 compared to that in Group B (P 0.025, 95% CI 1.07, 2.04). No severe toxicity or adverse event had been reported. The median follow-up time for Group A and Group B was 12.6 and 11.8 months, respectively. There was no statistical difference in PFS and OS. Concurrent chemoradiation by Tegafur-Uracil and carboplatin showed no difference in tumor response rate or treatment toxicity compared to carboplatin alone. The combination drugs might have benefit in poor prognostic patients such as the baseline Hb <10 gm/dL.

Nadroparine activated fibrinolysis and improvement of glomerular filtration rate in patients with FIGO IIB–IIIB cervical cancer treated with radiochemotherapy

(1) Evaluation of the influence of hemostatic disorders on renal function in patients with FIGO stage IIB-IIIB cervical cancer treated with radiochemotherapy. (2) Identifying methods of improving renal function in this patients group. Treatment design assumes the administration of a total radiation dose of 46-65 Gy and, additionally, cisplatin 40 mg/m2 every 7 days in patients with normal plasma creatinine level. Renal function was assessed with the aid of dynamic scintigraphy with glomerular filtration rate (GFR) evaluation. Analysis of serum hemostatic system covered D-dimers, PAP, PAI-1, tPA, FDP, F1+2 and TAT. The same hemostatic parameters were also evaluated in urine. The patients were divided into two groups: the study group - i.e. patients with affected GFR and the control group - with normal GFR. Half of study group patients, throughout the entire treatment, receive nadroparine 2850 units aXa/0.3 ml every 24 h during and 6 weeks after the treatment. There are significant decreases of GFR in control (median -9.7%) and study group without nadroparine (median -9.9%) and increase in the GFR (median 22.3%) in study group with nadroparine (p=0.0001). Plasma and urine hemostatic parameter analysis showed activation of fibrinolysis in patients treated with nadroparine and fibrinolysis inhibition in remaining groups. (1) Inhibition of fibrinolysis may cause subclinical renal insufficiency in patients with advanced cervical cancer. (2) Insufficiency increases after the end of radiochemotherapy in patients, as well with normal GFR as, with primary decreased GFR. (3) Application of nadroparine causes fibrinolysis activation, and increase in the GFR.