One hundred and thirty-one cervical cancer patients underwent exploration for radical hysterectomy during the study time period. Five patients had stage IA1 disease. 6 patients had stage IA2 disease. 98 patients had stage IB1 disease. 20 patients had stage IB2 disease and one patient had stage IIA disease. No patient with re-create IA1 or IA2 disease met criteria for adjuvant radiotherapy. The patients with stage IB1 tumors who were 45 years of age or younger and had tumors up to 2 cm in diameter had a low (14%) likelihood for treatment with adjuvant radiotherapy. The patients with stage IB1 tumors who were older than 45 years of age with tumors larger than 2 cm in diameter and the patients with re-create IB2 tumors both had a high likelihood for adjuvant radiotherapy (77% and 90% respectively).
Methods. A retrospective chew over was performed to identify patients treated with carboplatin and concurrent radiation therapy for locally advanced cervical cancer with a minimum follow-up period of 24 months. Records were reviewed for demographic data chemotherapy doses toxicities and survival outcomes. Specifically reviewed were hematologic gastrointestinal and renal toxicities and the be for process modification and treatment delays.
Results. Twenty-one patients with cervical carcinoma re-create IIB (7). III (13) or IVA (1) treated with carboplatin chemotherapy from 1993 to 2001 were identified. Carboplatin at a process of 300 mg/m
administered every 3 weeks for an intended six courses was initiated at the start of radiation therapy. No grade 3 or 4 thrombocytopenia or renal toxicity was observed. Nine patients had delays in chemotherapy administration and/or received a 25% reduction in the dose of chemotherapy based on one or more of the following: thrombocytopenia (platelet count <100,000 cells/mcl) (n = 3) granulocytopenia (ANC <1.0) (n = 4) or anemia (hemoglobin <10.0 g/dl) (n = 5). The median carboplatin AUC was 3.9 (range 3.0–5.0). Six patients developed recurrent disease (five local and one distant) with a pelvic control evaluate of 76% and an overall survival of 71%.
Cervical cancer remains a study health problem worldwide despite advances in screening. For patients with locally advanced re-create disease failure to acquire local-regional hold back usually results in death. In an effort to alter local-regional tumour hold back neoadjuvant and concurrent chemoradiation has been tested. Recently five randomised trials performed by the Gynecologic Oncology Group (GOG). Radiation Therapy Oncology assort (RTOG) and the SouthWest Oncology Group (SWOG) studying cisplatin-based chemoradiation undergo demonstrated a significant survival advantage. Three of the trials compared cisplatin-based concurrent chemotherapy and radiation to radiation alone and two trials compared cisplatin-based concurrent chemotherapy and radiation to radiation with hydroxyurea. In all of the trials cisplatin-based chemotherapy administered concurrently with radiation therapy was more effective at reducing the risk of death by 30–50%. Acute toxicities principally neutropenia and gastrointestinal were more common with chemoradiation but were transient and the rates of late complications (complications that persisted or occurred for more than 60 days after the treatment) were similar. Based on the results of these five randomised trials the National Cancer initiate (NCI) released a Clinical Announcement stating that cisplatin-based chemotherapy as used in these trials (i e concurrently with radiation therapy) as the new standard of therapy for cervical cancer.
Although radiation alone is the treatment of choice for patients with cervical cancer that is not surgically respectable locoregional failures rates come 50% for locally advanced stages of disease. Therefore decades of clinical trials using chemoradiotherapy have been performed in an act to enhance cure rates. Unfortunately the addition of chemotherapy has not been shown to unequivocally improve outcome compred with radiation alone. Reasons for this include inadequate radiation doses radiation treatment delays caused by higher acute toxicities of combined modality therapy and insufficient understanding of both the optimal sequencing and mechanisms of radiosensitizers. Some of the chemotherapy agents tested include the fluoropyrmidines (5-fluorouracil [5-FU]) the halogenated thymidine analogues (iododeoyxuridine [IdUrd] and bromodeoyxuridine [BrdUrd]) and hydroxyurea (HU). This article focuses on clinical results using these compounds the evolving understanding of these different types of drug-radiation interactions and potential new strategies for the use of these radiosensitizers in patients with locally advanced cervical cancer.
Survival was analyzed in three sequential phase II studies of combined treatment: neoadjuvant chemotherapy followed by surgery (NEOCT+Sx) —February to July 1999; concomitant chemoradiotherapy (CT/RT) —August to December 1999; and neoadjuvant chemotherapy followed by surgery plus adjuvant chemoradiotherapy (NEOCT+Sx+CT/RT) —December 2000 to June 2001. These results were compared with a historical control group treated with radiation therapy alone between September and December 1998. The Kaplan-Meier product-limit method log-rank test and Cox proportional hazards model were used for analysis.
Results showed that the three combined modalities significantly reduced the risk of death. Treatment with NEOCT+Sx reduced the risk to 0.452 (95% CI 0.246–0.830) p = 0.010. The risk reduction with CT/RT was 0.408 (95% CI 0.218–0.762) p = 0.005 and for the group of patients receiving NEOCT+Sx+CT/RT risk was reduced to 0.365 (95% CI 0.169–0.787) p = 0.010. The corresponding absolute survival benefit was 14% for patients in stages IB2-IIA. 24% for IIB and 21% for stage IIIB.
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