A phase I trial of tailored radiation therapy with concomitant cetuximab and cisplatin in the treatment of patients with cervical cancer: A gynecologic oncology group study

Moore, Kathleen N.; Sill, Michael W.; Miller, David S.; McCourt, Carolyn K.; Geest, Koen De; Rose, Peter G.; Cárdenes, Higinia R.; Farley, John H.; Schilder, Russell J.; Fracasso, Paula M.

doi:10.1016/j.ygyno.2012.08.030

Cited by 32 publications

(22 citation statements)

References 28 publications

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“…Chitapanarux et al found that grade 1-2 acute and late diarrhea were observed in 20 and 40% caused by chemotherapy, respectively, in their thirty metastatic or recurrent cervical cancer patients [31]. Moore et al studied patients receiving pelvic RT and showed that seven were treated with weekly cisplatin at doses of 30 and 40 mg/m 2 , with one dose-limiting toxicity, that is, febrile neutropenia with grade 3 diarrhea [32]. Rose et al reported that eleven patients received sixty-three doses of the topotecan/cisplatin combination therapy, nine with grade 2 diarrhea toxicity during pelvic radiation therapy in patients with locally advanced cervical cancer [33].…”

Section: Discussionmentioning

confidence: 99%

The Different Dose-Volume Effects of Normal Tissue Complication Probability Using LASSO for Acute Small-Bowel Toxicity during Radiotherapy in Gynecological Patients with or without Prior Abdominal Surgery

Lee

Huang

2014

BioMed Research International

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Purpose. To develop normal tissue complication probability (NTCP) model with least absolute shrinkage and selection operator (LASSO) to analyze dose-volume effects that influence the incidence of acute diarrhea among gynecological patients with/without prior abdominal surgery. Methods and Materials. Ninety-five patients receiving gynecologic radiotherapy (RT) were enrolled. The endpoint was defined as the grade 2+ acute diarrhea toxicity during treatment. We obtained the range of small-bowel volume in V4 Gy to V40 Gy of dose. Results. The number of patients experiencing grade 2+ acute diarrhea toxicity was 23/61 (38%) in the group without abdominal surgery (group 0) and 17/34 (50%) patients with abdominal surgery (group 1). The most significant predictor was found for the logistic NTCP model with V16 Gy as the cutoff dose for group 0 and V40 Gy for group 1. Logistic regression NTCP model parameters were TV10 ≈ 290 cc for V16 Gy and TV10 ≈ 75 cc for V40 Gy, respectively. Conclusion. To keep the incidence of grade 2+ acute small-bowel toxicity below 10%, we suggest that small-bowel volume above the prescription dose (V16 Gy) should be held to <290 cc for patients without abdominal surgery, and the prescription dose (V40 Gy) should be maintained <75 cc for patients with abdominal surgery.

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Section: Discussionmentioning

confidence: 99%

The Different Dose-Volume Effects of Normal Tissue Complication Probability Using LASSO for Acute Small-Bowel Toxicity during Radiotherapy in Gynecological Patients with or without Prior Abdominal Surgery

Lee

Huang

2014

BioMed Research International

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“…In an intention-to-treat analysis in NSCLC (Flex trial), tumor cell expression of EGFR (<40% vs. !40%) was not identified as a prognostic factor in relation to survival in the overall analysis (22). In cervical cancer, a recent phase I/II clinical trial in treatment na€ ve patients, documented the feasibility of concurrent cetuximab with cisplatin-based chemoradiotherapy to the pelvis; while the need for extended field radiotherapy, (EFRT) in combination with cisplatin and cetuximab was reported to be insufficiently tolerated (23). Objectives of the present trial were to assess the tolerance and the efficacy of the combining cetuximab with standard chemoradiotherapy, while also to assess outcome as a function of biologic parameters.…”

Section: Introductionmentioning

confidence: 99%

PIK3CA Pathway Mutations Predictive of Poor Response Following Standard Radiochemotherapy ± Cetuximab in Cervical Cancer Patients

Rochefordière

Kamal

Floquet

et al. 2015

Clinical Cancer Research

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Purpose: EGFR is frequently overexpressed in cervical cancer, suggesting EGFR blockade as a promising treatment approach. Cetuximab, an anti EGFR antibody, used conjointly with radiochemotherapy, was feasible in first-line treatment of cervix carcinoma limited to the pelvis.Experimental Design: This randomized phase II trial enrolled 78 FIGO stage IB2-IIIB cervical cancer patients to either cisplatinbased radiochemotherapy alone (arm B, n ¼ 38) or conjointly with a 6-week course of weekly cetuximab (arm A, n ¼ 40). Brachytherapy was given to the pelvic mass. Primary endpoint was disease-free survival (DFS) at 2 years. EGFR expression and targeted sequencing were performed in 54 of 78 patients.Results: Cetuximab over a 6-week period did not improve DFS at 24 months. At 31 months median follow-up, DFS was not significantly different (P ¼ 0.18). Complete response at 4 to 6 months was strongly predictive for excellent DFS (log-rank test; P < 0.001). PIK3CA, KRAS, and STK11 mutations were observed in 22%, 4%, and 2% of patients, respectively. No tumor with a PI3K pathway mutation showed complete response (0/8 in arm A and 0/6 in arm B), whereas 14 of 52 (27%) tumors without mutations did (P ¼ 0.021). PI3K pathway-mutated tumors showed a trend toward poorer DFS (P ¼ 0.06) following cetuximab (8/22) as compared with those following standard treatment only (6/18).Conclusions: Similar to patients with head and neck cancer, patients with cervical cancer showed no gain in DFS at 2 years following a combined treatment of cetuximab with radiochemotherapy. Although treatment tolerance and compliance were satisfactory, it remains to be demonstrated whether maintenance therapy with cetuximab could be beneficial in selected patient groups.

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“…Cetuximab is thought to function as a radiosensitizer contributing to a synergistic effect when it is combined with radiotherapy [14]. The combination of cetuximab and radiotherapy (CRT) has also been tested in several other EGFR-expressing squamous cell carcinomas including lung, anal, esophageal, and uterine cervix squamous cell carcinoma [15–18]. There is little data available on the safety and effectiveness of CRT in patients with advanced cSCC.…”

Section: Introductionmentioning

confidence: 99%

Locally Advanced and Unresectable Cutaneous Squamous Cell Carcinoma: Outcomes of Concurrent Cetuximab and Radiotherapy

Samstein

Lee

et al. 2014

Journal of Skin Cancer

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Background. Advanced age and immune dysfunction are risk factors for cutaneous squamous cell carcinoma (cSCC) and often render patients with locally-advanced disease medically inoperable or surgically unresectable, but potentially curable with radiotherapy. Concurrent chemotherapy and radiotherapy may not be well tolerated in this population, but another systemic therapy may improve disease control. Objective. Determine the tolerance and efficacy of concurrent cetuximab and radiotherapy (CRT) for patients with locally advanced and unresectable cSCC. Methods. Retrospective analysis of 12 patients treated with CRT for locally advanced and unresectable cSCC. Results. Patients were elderly and 75% had moderate-to-severe comorbidities, while 42% had immune dysfunction. Grades 3-4 adverse events were noted in 83% of patients; 67% required hospital admission for adverse events. Complete and partial response was noted in 36% and 27% (response rate, 64%). Stable and progressive disease was noted in 3 and 1 patients, respectively (disease control rate, 91%). Median progression-free and overall survival were 6.4 and 8.0 months, respectively. Limitations. Retrospective small-cohort, single-institution analysis. Conclusion. Patients selected for CRT were elderly, with comorbidities and immune dysfunction, but treatment responses were observed. Patients selected for this treatment approach have a poor prognosis with limited capacity for therapy; more effective treatment is needed.

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A phase I trial of tailored radiation therapy with concomitant cetuximab and cisplatin in the treatment of patients with cervical cancer: A gynecologic oncology group study

Cited by 32 publications

References 28 publications

The Different Dose-Volume Effects of Normal Tissue Complication Probability Using LASSO for Acute Small-Bowel Toxicity during Radiotherapy in Gynecological Patients with or without Prior Abdominal Surgery

The Different Dose-Volume Effects of Normal Tissue Complication Probability Using LASSO for Acute Small-Bowel Toxicity during Radiotherapy in Gynecological Patients with or without Prior Abdominal Surgery

PIK3CA Pathway Mutations Predictive of Poor Response Following Standard Radiochemotherapy ± Cetuximab in Cervical Cancer Patients

Locally Advanced and Unresectable Cutaneous Squamous Cell Carcinoma: Outcomes of Concurrent Cetuximab and Radiotherapy

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