Reply to phase 1 study of cetuximab in combination with 5-fluorouracil, cisplatin, and radiotherapy...
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10. Schiffer CA, Mangu PB, Wade JC, et al. Central venous catheter care for the patient with cancer: American Society of Clinical Oncol- ogy clinical practice guideline. J Clin Oncol. 2013;31:1357-1370. Victor Moreno, MD Medical Oncology Service La Paz University Hospital Madrid, Spain Rocio Garc ıa-Carbonero, MD Medical Oncology Service Virgen del Roc ıo University Hospital Seville, Spain Joan Maurel, MD Medical Oncology Service Barcelona Hospital Clinic Barcelona, Spain Jaime Feliu, MD Medical Oncology Service La Paz University Hospital Madrid, Spain DOI: 10.1002/cncr.28449, Published online November 14, 2013 in Wiley Online Library (wileyonlinelibrary.com) Reply to Phase 1 Study of Cetuximab in Combination With 5-Fluorouracil, Cisplatin, and Radiotherapy in Patients With Locally Advanced Anal Canal Carcinoma Feliu et al believe that local factors related to the central venous catheters (CVC) played a major role in the high incidence of venous thromboembolism (VTE) reported in our phase 1 trial. 1 Moreover, they claim that the inclusion of patients with concomitant severe illness favored the increased rates of VTE. They bring to light their own phase 2 experience in treating patients with locally advanced anal canal carcinoma with pelvic chemoradiation based on the use of mitomycin-C plus panitumumab, in which no cases of VTE were reported to have occurred. In addition, they refer to the results of two phase 2 trials that have been published only in abstract form. Our reasons for disagreeing with Feliu et al are manifold. First, comparison across the trials they refer to is not trivial because different treatment strategies and agents were administered. Full reports of these trials are required to draw any conclusion. We believe the type of catheter used in our study did not influence the rate of VTE. The alteration of peripherally inserted central cathe- ters to implanted CVCs in 12 patients treated with the recommended phase 2 dose did not appear to have any impact on the VTE rate, which continued to occur in 25%, or 3 of 12 patients. Conversely, the use of agents with potential risk for VTE (cisplatin and cetuximab) in combination may be an issue. In our experience with the use of only cisplatin-based chemoradiation in 86 patients with locally advanced anal canal carcinoma, no patient developed VTE. 2 Cumulative toxicities may be relevant. In our trial, the majority of patients received full treatment and developed severe toxicities, and the majority of the cases of VTE occurred after the second cycle of chemotherapy. Conversely, in the ACCORD 16 trial, 3 which is more similar to ours, no VTE occurred, but only 8 of the 16 en- rolled patients completed treatment. In fact, a constella- tion of factors such as diarrhea, infection, neutropenia, and hospitalization may have played a role. Secondly, severe comorbidities or cardiovascular disease were exclusion criteria in our trial. The Khorana et al predictive model for chemotherapy- associated thrombosis was applied in all patients. 4 Only 3 of 23 patients were found to have an interme- diated risk for VTE, and the remaining 20 patients were found to be at low risk for developing VTE. In conclusion, local factors and comorbidities do not appear to have played a major role in the high VTE rate found in our study. 1 CONFLICT OF INTEREST DISCLOSURES The authors made no disclosures. REFERENCES 1. Olivatto LO, Vieira FM, Pereira BV, et al. Phase 1 study of cetuxi- mab in combination with 5-fluorouracil, cisplatin, and radiotherapy in patients with locally advanced anal canal carcinoma. Cancer. 2013; 119:2973-2980. 2. Olivatto LO, Cabral V, Rosa A, et al. Mitomycin-C– or cisplatin- based chemoradiotherapy for anal canal carcinoma: long-term results. Int J Radiat Oncol Biol Phys. 2011;79:490-495. 3. Deutsch E, Lemanski C, Paris E, et al. Cetuximab plus radio- chemotherapy in locally advanced anal cancer: Interim results of the French multicenter phase II trial ACCORD16 [Abstract]. J Clin Oncol. 2011;29(suppl 15): Abstract 40983. 4. Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy- associated thrombosis. Blood. 2008;111:4902-4907. Luis Olivatto, MD, MSc Division of Clinical Oncology National Cancer Institute Rio de Janeiro, Brazil Carlos Gil Ferreira, MD, PhD Coordination of Clinical Research National Cancer Institute Rio de Janeiro, Brazil DOI: 10.1002/cncr.28448, Published online November 14, 2013 in Wiley Online Library (wileyonlinelibrary.com) Correspondence 456 Cancer February 1, 2014
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Transcript of Reply to phase 1 study of cetuximab in combination with 5-fluorouracil, cisplatin, and radiotherapy...
10. Schiffer CA, Mangu PB, Wade JC, et al. Central venous cathetercare for the patient with cancer: American Society of Clinical Oncol-ogy clinical practice guideline. J Clin Oncol. 2013;31:1357-1370.
Victor Moreno, MDMedical Oncology Service
La Paz University HospitalMadrid, Spain
Rocio Garc�ıa-Carbonero, MDMedical Oncology Service
Virgen del Roc�ıo University HospitalSeville, Spain
Joan Maurel, MDMedical Oncology ServiceBarcelona Hospital Clinic
Barcelona, Spain
Jaime Feliu, MDMedical Oncology Service
La Paz University HospitalMadrid, Spain
DOI: 10.1002/cncr.28449, Published online November 14, 2013in Wiley Online Library (wileyonlinelibrary.com)
Reply to Phase 1 Study ofCetuximab in Combination With5-Fluorouracil, Cisplatin, andRadiotherapy in Patients WithLocally Advanced Anal CanalCarcinoma
Feliu et al believe that local factors related to the centralvenous catheters (CVC) played a major role in the highincidence of venous thromboembolism (VTE) reported inour phase 1 trial.1 Moreover, they claim that the inclusionof patients with concomitant severe illness favored theincreased rates of VTE. They bring to light their ownphase 2 experience in treating patients with locallyadvanced anal canal carcinoma with pelvic chemoradiationbased on the use of mitomycin-C plus panitumumab, inwhich no cases of VTE were reported to have occurred. Inaddition, they refer to the results of two phase 2 trials thathave been published only in abstract form.
Our reasons for disagreeing with Feliu et al aremanifold. First, comparison across the trials they refer tois not trivial because different treatment strategies andagents were administered. Full reports of these trials arerequired to draw any conclusion. We believe the type ofcatheter used in our study did not influence the rate ofVTE. The alteration of peripherally inserted central cathe-ters to implanted CVCs in 12 patients treated with therecommended phase 2 dose did not appear to have any
impact on the VTE rate, which continued to occur in25%, or 3 of 12 patients. Conversely, the use of agentswith potential risk for VTE (cisplatin and cetuximab) incombination may be an issue. In our experience with theuse of only cisplatin-based chemoradiation in 86 patientswith locally advanced anal canal carcinoma, no patientdeveloped VTE.2
Cumulative toxicities may be relevant. In our trial,the majority of patients received full treatment anddeveloped severe toxicities, and the majority of the casesof VTE occurred after the second cycle of chemotherapy.Conversely, in the ACCORD 16 trial,3 which is moresimilar to ours, no VTE occurred, but only 8 of the 16 en-rolled patients completed treatment. In fact, a constella-tion of factors such as diarrhea, infection, neutropenia,and hospitalization may have played a role.
Secondly, severe comorbidities or cardiovasculardisease were exclusion criteria in our trial. TheKhorana et al predictive model for chemotherapy-associated thrombosis was applied in all patients.4
Only 3 of 23 patients were found to have an interme-diated risk for VTE, and the remaining 20 patientswere found to be at low risk for developing VTE. Inconclusion, local factors and comorbidities do notappear to have played a major role in the high VTErate found in our study.1
CONFLICT OF INTEREST DISCLOSURESThe authors made no disclosures.
REFERENCES1. Olivatto LO, Vieira FM, Pereira BV, et al. Phase 1 study of cetuxi-
mab in combination with 5-fluorouracil, cisplatin, and radiotherapyin patients with locally advanced anal canal carcinoma. Cancer. 2013;119:2973-2980.
2. Olivatto LO, Cabral V, Rosa A, et al. Mitomycin-C– or cisplatin-based chemoradiotherapy for anal canal carcinoma: long-term results.Int J Radiat Oncol Biol Phys. 2011;79:490-495.
3. Deutsch E, Lemanski C, Paris E, et al. Cetuximab plus radio-chemotherapy in locally advanced anal cancer: Interim results of theFrench multicenter phase II trial ACCORD16 [Abstract]. J ClinOncol. 2011;29(suppl 15): Abstract 40983.
4. Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW.Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood. 2008;111:4902-4907.
Luis Olivatto, MD, MScDivision of Clinical Oncology
National Cancer InstituteRio de Janeiro, Brazil
Carlos Gil Ferreira, MD, PhDCoordination of Clinical Research
National Cancer InstituteRio de Janeiro, Brazil
DOI: 10.1002/cncr.28448, Published online November 14, 2013in Wiley Online Library (wileyonlinelibrary.com)
Correspondence
456 Cancer February 1, 2014
