A phase II study of weekly neoadjuvant chemotherapy followed by radical chemoradiation for locally advanced cervical cancer

McCormack, Mary; Kadalayil, Latha; Hackshaw, Allan; Hall-Craggs, M. A.; Symonds, R.P.; Warwick, Violet; Simonds, Hannah; Fernando, Indrajit; Hammond, M. Elizabeth; James, L.E; Feeney, Amanda; Ledermann, Jonathan A.

doi:10.1038/bjc.2013.230

Cited by 105 publications

(97 citation statements)

References 19 publications

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“…The CxII (McCormack et al) trial used a novel approach of administering weekly carboplatin and paclitaxel chemotherapy for six weeks followed immediately by standard CRT commencing in week seven. 11 The results from this trial confirm that a short course of dose-dense weekly NACT with carboplatin and paclitaxel, followed by radical CRT, is feasible with acceptable toxicity. Hence we have taken a similar study in our setup to evaluate role of neo-adjuvant chemotherapy in cervical cancer patients with paclitaxel and carboplatin with reducing the number of neoadjuvant chemotherapy cycles to 3 instead of 6 cycles.…”

Section: Discussionsupporting

confidence: 62%

Prospective comparative study of dose dense neo-adjuvant chemotherapy followed by chemo-radiation and definitive chemo-radiation alone in stage IB2-IVA cervical cancer

Karpurmath¹,

Nimma²,

Narayanan³

et al. 2016

Int J Reprod Contracept Obstet Gynecol

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INTRODUCTIONCervical cancer is the fourth most common cancer among women worldwide. 1 It is the second most common diagnosed cancer and third most leading cause of death in less developed countries. India accounts for 25% of cervical cancer deaths in less developed countries. Concurrent chemo radiotherapy (CRT) has become the standard of care for cervical cancer patients from stages 1B2 to IVA. 2 There is 6% improvement in the survival rates with the addition of chemotherapy to radiation as per the meta-analysis of 13 trials comparing chemoradiation and radiation alone. 3 There were no major advances in the treatment of cancer cervix after definitive chemo-radiation became the standard of care. There are still potential therapeutic advantages of giving chemotherapy before radiotherapy to reduce tumour size and control micro metastatic disease. A number of randomised trials have explored the use of neo-adjuvant chemotherapy (NACT) because of impressive response rates. As per the meta-analysis of neo-adjuvant chemotherapy for locally advanced cervical cancer 2003, there was no benefit for neo-adjuvant chemotherapy but the trials which used shorter cycle lengths showed 7% Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. ABSTRACT Background:The standard of care for locally advanced cervical cancer is chemo-radiation. Role of neo-adjuvant chemotherapy not clear yet. Dose dense, short-term neo-adjuvant chemotherapy with early initiation of radiotherapy has shown survival benefit but randomised trials not available yet. Hence this study was done for feasibility of neoadjuvant chemotherapy and for its comparison with the standard chemo-radiation. Methods: Cervical cancer patients not randomly assigned into two arms. Arm A received 3 cycles NACT of paclitaxel and carboplatin weekly. All patients of arm A after NACT and arm B received EBRT on linear accelerator for a dose of 4500-5000cGy in 23-25 fractions with concurrent cisplatin 40mg/m2 followed by 3 applications of HDR intracavitary brachytherapy of 700 or 800cGy respectively. All patients were assessed clinically and radiologically with MRI after completion of CTRT and at follow up of 6 weeks. Results: A total of 15 patients treated in each arm. Stage IIB and IIIB constituted 93% of the patients, well matched in both the arms. The CR rate at follow up of 6 weeks after NACT was 73% compared to only 46.7% in arm B. Neutropenia of grade 3 were seen equally in both the arms and grade 2 neutropenia was seen in about 60% patients in arm A compared to only 20% patients in arm B which was manageable without growth factors. Conclusions: Dose dense neo-adjuvant chemotherapy is a feasible and effective option in treating cancer cervix.

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Section: Discussionsupporting

confidence: 62%

Prospective comparative study of dose dense neo-adjuvant chemotherapy followed by chemo-radiation and definitive chemo-radiation alone in stage IB2-IVA cervical cancer

Karpurmath¹,

Nimma²,

Narayanan³

et al. 2016

Int J Reprod Contracept Obstet Gynecol

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“…According to McCormack, the overall and progression-free survivals at 3 years were 67 % (95 % CI 51-79) and 68 % (95 % CI 51-79), respectively, after use of weekly NCAT for 6 weeks. The Grade 3 and 4 toxicities were 20 % during NACT-11 % were hematological and 9 % were non-hematological-and 52 % during CRT-41 % were hematological and 22 % were non-hematological [14].…”

Section: Discussionmentioning

confidence: 94%

Pros and Cons of Adding of Neoadjuvant Chemotherapy to Standard Concurrent Chemoradiotherapy in Cervical Cancer: A Regional Cancer Center Experience

Narayan

Sharma

Kapoor

et al. 2015

J Obstet Gynecol India

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Background The present study summarizes the results of treatment in the form of disease-free survival and overall survival in bulky stage IB2 and locally advanced (stages II-IVA) squamous cell carcinoma of the uterine cervix. The treatment has been given in the form of NACT followed by CCRT in one arm and CCRT in the other arm. The grade 3/4 hematologic toxicities were more in the NACT group than CCRT (p \ 0.001) while the non-hematological toxicity was not significant; the TPF group experienced more toxicity than PF (p = 0.029). This treatment regimen is feasible as evidenced by the acceptable toxicity of NACT and by the high compliance to radiotherapy. The grade 3/4 hematologic toxicities were more in NACT groups than CCRT (p \ 0.001); the TPF group experienced more toxicity than PF (p = 0.029). Materials and Methods

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“…Grade 3-4 hematologic toxicity was seen in about 20% of patients. These observations are encouraging [52,53] and need confirmation in a randomized study.…”

Section: Dose-dense Nact Prior To Ccrtmentioning

confidence: 88%

Integrating Chemotherapy in the Management of Cervical Cancer: A Critical Appraisal

Kumar

Gupta

2016

Oncology

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The management of locally advanced cervix cancer has undergone a paradigm shift during the last decade. Concurrent chemoradiation (CCRT) (with cisplatin alone or in combination) is currently the standard treatment approach. CCRT results in a 5-year overall survival rate of 66% and a disease-free survival of 58%. About 30-40% of patients with locally advanced cervical cancer fail to achieve complete response to CCRT; alternative approaches are needed to improve the outcome for such patients. Weekly paclitaxel and carboplatin for 4-6 weeks as dose-dense chemotherapy prior to CCRT could be one such potential approach. The role of adjuvant chemotherapy after CCRT in patients with positive lymph nodes, larger tumor volume and stage III-IVA disease needs further exploration. Adjuvant chemotherapy is also being investigated for early-stage (stages IA2, IB1 or IIA) cervical cancer with presence of risk factors such as lymph node metastasis, lymphovascular space invasion and invasion depth of more than 10 mm, microscopic parametrial invasion, non-squamous histology and positive surgical margins. For patients with early-stage disease (IA2-IIA), short-course chemotherapy prior to surgery is associated with an improved outcome in many studies. Neo-adjuvant chemotherapy followed by fertility preservation surgery is feasible in carefully selected young patients with bulky stage IB1 disease. Recently, a number of molecular pathways have been identified as potential therapeutic targets. Bevacizumab - an inhibitor of vascular endothelial growth factor - is associated with improved survival in patients with recurrent/metastatic cervical cancer. Whether bevacizumab and other similar novel agents targeting molecular pathways could be used in front-line treatment along with cytotoxic chemotherapy is likely to be an area of research in future studies.

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A phase II study of weekly neoadjuvant chemotherapy followed by radical chemoradiation for locally advanced cervical cancer

Cited by 105 publications

References 19 publications

Prospective comparative study of dose dense neo-adjuvant chemotherapy followed by chemo-radiation and definitive chemo-radiation alone in stage IB2-IVA cervical cancer

Prospective comparative study of dose dense neo-adjuvant chemotherapy followed by chemo-radiation and definitive chemo-radiation alone in stage IB2-IVA cervical cancer

Pros and Cons of Adding of Neoadjuvant Chemotherapy to Standard Concurrent Chemoradiotherapy in Cervical Cancer: A Regional Cancer Center Experience

Integrating Chemotherapy in the Management of Cervical Cancer: A Critical Appraisal

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