Toxicity Profile of Double-agent Adjuvant Chemotherapy after Concurrent Chemoradiation and Brachytherapy in Locally Advanced Cervical Cancer: Comparison with Standard Chemoradiation Protocol

Abstract

Introduction: Carcinoma cervix is the most common gynecological malignancy in India and a major cause of cancer mortality and morbidity in the females despite Concurrent chemoradiotherapy (CCRT). Attempts are on to improved overall survival by addition of adjuvant chemotherapy (ACT) to CCRT. Aim: The aim of this study is to establish toxicity profile of double-agent ACT after CCRT and ICRT in locally advanced cervical cancer (LACC) and to compare it with standard chemoradiation protocol. Materials and Methods: Patients were randomized into two arms: in conventional arm (Arm 1, n = 23), patients received a standard protocol of weekly injection cisplatin 40 mg/m 2 concurrently with pelvic external beam radiotherapy (5040cGy/28 fractions) followed by ICRT (03 fractions of 7 Gy each). In interventional arm (Arm 2, n = 24), patients received CCRT/ICRT protocol; and were further offered ACT with three cycles of consolidation chemotherapy using injection paclitaxel and injection carboplatin every 3 weeks after CCRT and ICRT. Results: The incidence of anemia was 14/23 (50% Grade 1) in Arm 1 and 12/24 in Arm 2 (17% Grade 1, rest higher grade). In Arm 2, 37% of patients had ≥Grade 2 neuropathy and 16% of patients had Grade 1 alopecia, whereas nil incidence was reported in Arm 1 (P = 0.005 and 0.04, respectively). Grade 3 neutropenia was observed in 4/23 (17%) patients of Arm 1 and 8/24 patients (33%) of Arm 2. None of the patients in Arm 1 required indoor supportive care while 4/24 patients (17%) were managed as an indoor patient. Among late toxicities, in Arm 2, the incidence of Grade 2 and Grade 3 anemia was 42%, whereas in Arm 1, its incidence was 22%. In Arm 1, no patient exhibited features of neuropathy, whereas, in Arm 2, 12/24 (50%) of the patients had neuropathy (P value for these two late events was <0.05 statistically significant). No therapy-induced mortality was noted. Conclusion: Exhibition of ACT with injection Paclitaxel and injection carboplatin in locally advanced carcinoma cervix is a technically viable option with manageable toxicity.

Integration of Consolidation Chemotherapy After Concurrent Chemoradiation in the Treatment of Locally Advanced Uterine Cervical Cancer

“…Grade 2 was seen in a mean percentage of 90.4% of study population, whereas grade 3 neuropathy was seen in a mean percentage of 9.5%. This finding was similar to that seen in study by Pandya et al [ 23 ].…”

“…In developing countries including India, studies incorporating the use of adjuvant chemotherapy (ACT) in LACC after CCRT is done as an attempt to improve survival [ 23 ]. In our study, the idea behind giving consolidation chemotherapy was to consolidate local control of the disease achieved by concomitant chemoradiotherapy and to eradicate potential distant micro-metastasis.…”

Adjuvant Systemic Therapy after Chemoradiation and Brachytherapy for Locally Advanced Cervical Cancer: A Systematic Review and Meta-Analysis

“…This was 5-fluorouracil in five [ 18 , 19 , 22 , 23 , 24 , 35 ], gemcitabine in four studies [ 11 , 20 , 21 , 34 , 37 ]. In 12 studies, adjuvant systemic therapy was 3–6 cycles of a platinum derivate (carboplatin [ 17 , 25 , 27 , 29 , 30 , 31 , 32 , 33 , 40 ], cisplatin [ 49 ], cisplatin or carboplatin [ 28 ] or nedaplatin [ 32 ] with a taxane (paclitaxel in 11 [ 17 , 25 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 40 , 50 ], docetaxel in 1 [ 49 ]). The remaining eight studies investigated adjuvant platinum derivates ( N = 2) [ 38 , 47 ], pyrimidine antagonists as monotherapy ( N = 2) [ 26 , 36 ], cis- platin-ifosfamide ( N = 1) [ 42 , 43 , 44 , 45 , 46 ], 5-fluorouracil with interferon and retinoic acid ( N = 1) [ 48 ], ipilimumab [ 41 ] and pembrolizumab [ 39 ].…”

“…a The number of patients reported in this table represents the number of patients that could be included in the current study as either a control group (CRT) or experimental group (CRT + AdjTx); patients who were treated with other regimens (e.g., radiotherapy only) are not included in the current study and not represented here. b Age reported as median (range), or if unavailable, mean (Lorvidhaya et al [ 26 ], Pandya et al [ 29 ], Tu et al [ 31 ], Boardman et al [ 33 ] and Duska et al [ 39 ]). c Mexico, Argentina, India, Panama, Bosnia Herzegovina, Peru, Thailand, Pakistan, Australia.…”