|Year : 2020 | Volume
| Issue : 1 | Page : 17-24
Modified 3-weekly cisplatin or cisplatin-5-fluorouracil 5-day infusion as the concurrent chemoradiotherapy regimen in locally advanced squamous cell carcinoma of the head and neck: Comparison of efficacy and toxicity
Nai-Wen Su1, Kaun-Jer Tsai1, Yi-Shing Leu2, Jehn-Chuan Lee2, Chung-Ji Liu3, Chieh-Yuan Cheng3, Jiun-Sheng Lin3, Yu-Jen Chen4, Shih-Hua Liu4, Chun-How Chen4, Yi-Fang Chang5
1 Division of Medical Oncology and Hematology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
2 Department of Otorhinolaryngology, MacKay Memorial Hospital, Taipei, Taiwan
3 Department of Oral and Maxillofacial Surgery, MacKay Memorial Hospital, Taipei, Taiwan
4 Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan
5 Division of Medical Oncology and Hematology, Department of Internal Medicine; Department of Medical Research, Good Clinical Research Center, MacKay Memorial Hospital, Taipei, Taiwan
|Date of Submission||30-Apr-2019|
|Date of Decision||01-Oct-2019|
|Date of Acceptance||11-Oct-2019|
|Date of Web Publication||2-Mar-2020|
Dr. Yi-Fang Chang
Division of Medical Oncology and Hematology, Department of Internal Medicine, MacKay Memorial Hospital, No. 92, Section 2, Zhongshan N Road, Zhongshan District, Taipei 90104
Source of Support: None, Conflict of Interest: None
Background: Concurrent chemoradiotherapy (CCRT) is an important therapeutic strategy in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). We evaluated the efficacy and toxicity of two CCRT regimens in treating LA-SCCHN. Materials and Methods: LA-SCCHN patients receiving CCRT with either a modified 3-weekly cisplatin 75 mg/m2 (Group A, n = 86) or 5-day continuous infusion of cisplatin 12 mg/m2 plus 5-fluorouracil (5-FU) 600 mg/m2 (Group B, n = 87) were enrolled. The Kaplan−Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and locoregional recurrence-free survival (LRFS). Univariate and multivariate analyses were performed using Cox proportional hazard models to assess correlations between clinical parameters and survival. Results: With a median of 35.8 months' follow-up, the median OS and PFS in Group A and Group B were 65.9 versus 55.0 months (P = 0.546) and 34.6 versus 33.3 months (P = 0.948), respectively. LRFS was not reached in either group. Group B patients had more Grade 3−4 mucositis (53.7% vs. 32.28%, P= 0.001) and dermatitis (49.8% vs. 21.5%, P= 0.0001). Trends of higher incidence rates of Grade 3−4 hematologic and renal toxicity were observed in Group A. After statistical adjustment, higher disease stage (Stage IVb) (hazard ratio [HR] = 6.657, 95% confidence interval [CI] 1.786−24.81, P= 0.005) and pretreatment anemia (hemoglobin <13 g/dL) (HR = 1.896, 95% CI 1.063−3.391, P= 0.030) were associated with poor OS. Conclusion: A 5-day cisplatin-5-FU regimen was associated with more frequent Grade 3−4 mucositis and dermatitis than a 3-weekly cisplatin regimen. A multiagent CCRT regimen did not provide survival benefits but increased adverse events.
Keywords: Cisplatin, concurrent chemoradiotherapy, squamous cell carcinoma of the head and neck, toxicity
|How to cite this article:|
Su NW, Tsai KJ, Leu YS, Lee JC, Liu CJ, Cheng CY, Lin JS, Chen YJ, Liu SH, Chen CH, Chang YF. Modified 3-weekly cisplatin or cisplatin-5-fluorouracil 5-day infusion as the concurrent chemoradiotherapy regimen in locally advanced squamous cell carcinoma of the head and neck: Comparison of efficacy and toxicity. J Cancer Res Pract 2020;7:17-24
|How to cite this URL:|
Su NW, Tsai KJ, Leu YS, Lee JC, Liu CJ, Cheng CY, Lin JS, Chen YJ, Liu SH, Chen CH, Chang YF. Modified 3-weekly cisplatin or cisplatin-5-fluorouracil 5-day infusion as the concurrent chemoradiotherapy regimen in locally advanced squamous cell carcinoma of the head and neck: Comparison of efficacy and toxicity. J Cancer Res Pract [serial online] 2020 [cited 2020 Jun 4];7:17-24. Available from: http://www.ejcrp.org/text.asp?2020/7/1/17/279752
| Introduction|| |
Concurrent chemoradiotherapy (CCRT) is a cornerstone of treatment for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Concomitant chemotherapy, in combination with radiotherapy (RT), has been reported to provide absolute 5-year survival benefits of 6.5% in both postoperative adjuvant and definitive settings., Three-weekly cisplatin 100 mg/m2 during RT is generally accepted to be the standard regimen worldwide. However, less than two-thirds of patients have been reported to be able to complete the prescribed three cycles of chemotherapy in clinical trials.,, In addition, the significant acute and chronic toxicities caused by CCRT, which compromise the quality of life of patients presenting with SCCHN, are of great concern., Different concomitant chemotherapy regimens have been investigated with the goal of improving treatment efficacy and minimizing their toxicity.,,,,, In our previous study, we compared two cisplatin and 5-fluorouracil (5-FU) CCRT regimens and concluded that a higher dose regimen resulted in elevated toxicity despite survival outcomes remaining the same. As a result, we use a lower dose of cisplatin and 5-FU in the routine treatment of SCCHN. On the other hand, we modified the dose of a 3-weekly cisplatin regimen to 75 mg/m2, which has also been adopted in some Asian countries to enhance tolerability and compliance to CCRT., In the present study, we report our experience of using the aforementioned CCRT regimens for patients with LA-SCCHN at a single institution with regards to treatment outcomes and toxicity profiles.
| Materials And Methods|| |
This retrospective cohort study was approved on Aug-4th 2015 by MacKay Memorial Hospital Institutional Review Board (MMH-IRB) with the approval number 15MMHIS053. Informed consent form from patients was not required in this approved study. Patients presenting with pathologically confirmed, newly diagnosed, nonmetastatic LA-SCCHN (Stage III, IVa, IVb) were enrolled in the study. The primary tumors in all cases arose from the oral cavity, oropharynx, hypopharynx, or larynx. All patients had a detailed history of physical examinations, including fibroscopy and imaging studies such as computed tomography, magnetic resonance imaging, abdominal ultrasonography, and bone scintigraphy. Cancer staging was made according to the American Joint Committee on Cancer 7th edition. Patients receiving either definitive or postoperative adjuvant CCRT were eligible to participate in the study. After completing treatment, regular outpatient follow-up visits were arranged, consisting of monthly visits in the 1st year, visits every 3 months in the following 2 years, and every 6 months thereafter. In the event that the disease recurred, the treatment was provided at the discretion of the treating physician as per clinical conditions after considering the patient's best interests.
The choice of treatment was made after a multidisciplinary team discussion, and the final decision was made by the patient and the treating physician. The patients who received curative surgery underwent local tumor-wide excision and standard unilateral or bilateral neck dissection. All surgically treated patients had R0 resection. Postoperative CCRT was performed for patients presenting with any major pathologic features, including surgical margin or extranodal extensions. Patients with two or more minor pathologic features, including a close surgical margin (1−5 mm), poorly differentiated histology, lymphovascular invasion, perineural invasion, and/or multiple positive lymph nodes (N2b or higher nodal disease) also received adjuvant CCRT at our institution. Induction chemotherapy was performed prior to definitive CCRT, and the regimens included cisplatin and 5-FU with or without docetaxel.
The mode of irradiation used in all patients was intensity-modulated RT. The daily radiation dose was 1.8−2 Gy, and it was delivered in 5 fractions per week. The highest radiation dose was 66 Gy to the primary tumor sites and metastatic lymph nodes, and 60 Gy or 54 Gy to the lower risk areas in postoperative CCRT. In the definitive CCRT setting, the highest dose was 70 Gy, followed by 66 and 60 Gy. CCRT-related toxicity can prolong the RT treatment time and is regarded to be a poor prognostic factor. When completing whole RT treatment took longer than 50 days, it was defined as RT prolongation.
Two chemotherapy regimens were compared. One consisting of 3-weekly cisplatin 75 mg/m2 delivered on day 1, 22, and 43 during RT (Group A), and the other consisting of cisplatin 12 mg/m2 and 5-FU 600 mg/m2 delivered as a continuous infusion for 120 h at week 1 and week 5 during RT (Group B). The patients were adequately hydrated and given the same antiemetic agents, including palonosetron, aprepitant, and dexamethasone. The patients were followed up at the outpatient department weekly during RT. Toxicities were recorded according to the Common Terminology Criteria for Adverse Events version 4.03 and managed appropriately.
End points and statistical analysis
All of the time-related endpoints were counted from the date of the first treatment to the date of the occurrence of events. The data cutoff date was December 31, 2016. Patients who were lost to follow-up and those with no events until the data cut-off date were recorded as being “censored.” Two years of follow-up was required for all living patients to be included in the analysis. Any cause of death was accounted for in the overall survival (OS). Events consisting of locoregional or distant recurrence, second primary cancer, disease progression after initial treatment, or any cause of death were accounted for in the progression-free survival (PFS). The events for locoregional recurrence-free survival (LRFS) were primary tumor and/or regional lymph node recurrence or progression. Clinical and pathological characteristics between the two groups were calculated using two-sample t-tests or Fisher's exact test. The OS, PFS, and LRFS were analyzed using the Kaplan−Meier method. We also analyzed the clinical parameters including age (<50 vs. ≥50 years), the Eastern Cooperative Oncology Group performance status (0 vs. 1), disease Stage (III vs. IVa vs. IVb), primary tumor site (oral cavity vs. others), prolonged RT duration (<50 days vs. ≥50 days), pretreatment hemoglobin (Hb) level (<13 vs. ≥13 g/dL), and chemotherapy regimen (3-weekly cisplatin vs. cisplatin/5-FU), factors which may have affected survival outcomes. Univariate and multivariate analyses of these parameters were evaluated using Cox-proportional hazard models. The statistical analyses and preparation of graphs were performed and created using SPSS (version 22) (IBM Corp, Armonk, NY, USA) and SAS (version 9.4) (SAS Institute Inc., Cary, NC, USA).
| Results|| |
Patient characteristics and overall treatment results
From May 2010 to December 2014, a total of 173 patients were included in our analysis. Eighty-six patients received postoperative CCRT, and the others received definitive CCRT. The baseline patient characteristics were balanced between the two chemotherapy groups [Table 1]. At a median follow-up of 35.8 months (interquartile range: 15.1−56.8 months), the median OS of the overall patient population was 65.9 months (95% confidence interval [CI]: 46.2−85.8 months), and the median PFS was 34.6 months (95% CI: 19.6−49.6 months). At the last follow-up date, there were 41 and 42 deaths in Group A and Group B, respectively. The events of PFS in the two groups are shown in [Table 2].
|Table 1: Clinical and pathologic characteristics of the two concurrent chemoradiotherapy regimen groups|
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Comparison of toxicity profiles
There were two and three CCRT-related deaths in Group A and Group B, respectively. The major Grade 3 and 4 toxicity profiles of the two regimens are summarized in [Table 3]. Group B had higher incidence rates of Grade 3−4 mucositis (53.7% vs. 32.3%, P = 0.002) and dermatitis (49.8% vs. 21.5%, P = 0.0001) than Group A. There was a trend of increased Grade 3−4 elevated serum creatinine in Group A (5.8% vs. 1.2%, P = 0.099). Nineteen patients in Group A (22.1%; patient refusal: 2; renal function deterioration: 10; neutropenia: 6; and mucositis: 1) and 11 patients in Group B (12.6%; mucositis: 7; dermatitis: 3; and neutropenia: 1) could not complete the defined chemotherapy dosing schedule. One patient in each group could not complete the defined RT dose. Forty patients (46.5%) in Group A and 46 patients (52.9%) in Group B had RT prolongation.
Comparison of the treatment efficacy
The median PFS in Group A was 34.6 months (95% CI: 10.9−58.3 months) compared to 33.3 months (95% CI: 12.4−54.3 months) (P = 0.948) [Figure 1]a in Group B. The median OS was 65.9 months (95% CI: 47.2−84.8 months) in Group A compared to 55 months (95% CI: 33.7−76.3 months) in Group B (P = 0.546) [Figure 1]b. The median LRFS was not reached in either group (P = 0.806) [Figure 1]c. The estimated 1-year, 2-year, and 3-year PFS, OS, and LRFS rates were not significantly different between the two groups [Table 4]. Univariate analysis of OS showed that in patients with Stage IVb and pretreatment Hb level <13 g/dL, the outcomes were significantly worse. In multivariate analysis, the hazard ratio (HR) of OS was 6.657 (95% CI: 1.786−24.81, P = 0.005) for patients with Stage IVb disease and 1.896 (95% CI: 1.063−3.391, P = 0.003) for patients with pretreatment Hb level <13 g/dL compared to the reference group [Table 5]. With regards to PFS, the outcome was significantly worse only in the patients with Stage IVb disease in both univariate and multivariate analyses. The HR of PFS was 8.868 (95% CI: 1.784−44.07, P = 0.008) for patients with Stage IVb disease compared to the reference group [Table 6]. The choice of chemotherapy regimen did not significantly influence the OS and PFS in this study.
|Figure 1: The Kaplan−Meier survival curve of the two chemotherapy regimens. (a) progression-free survival; (b) overall survival; (c) locoregional recurrence-free survival. Group A denotes 3 weekly cisplatin. Group B denotes cisplatin plus 5-fluorouracil. P < 0.05 represents statistical significance|
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|Table 4: 1-year, 2-year and 3-year progression-free survival, overall survival and locoregional recurrence-free survival of the two chemotherapy groups|
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|Table 5: Univariate and multivariate analysis of parameters related to overall survival|
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|Table 6: Univariate and multivariate analysis of parameters related to progression-free survival|
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| Discussion|| |
It is always a clinical challenge to choose the appropriate chemotherapy regimen in combination with radiation when treating LA-SCCHN patients. Most previous studies comparing different CCRT regimens have been retrospective in nature.,,,,,,,, In this retrospective cohort study, we compared the treatment efficacy and toxicity between two regimens in both definitive and postoperative CCRT settings. Other studies have also included patients with or without upfront surgery; however, they have not detailed the pathologic characteristics, which may affect the treatment outcomes.,,,,, In the current study, the clinical and pathological parameters were well balanced between the two groups. With regards to the toxicity profiles, the rates of Grade 3−4 mucositis and dermatitis were significantly increased in the patients receiving cisplatin/5-FU, which is consistent with previous studies.,, However, we found higher incidence rates of chemotherapy-related Grade 3−4 hematologic toxicity [Table 3] and elevated serum creatinine (5.8% vs. 1.2%, P = 0.099) in the patients receiving 3-weekly cisplatin. Rades et al. demonstrated that multiagent chemotherapy provided no benefits on survival and disease control.,, However, the incidence of chemotherapy-related toxicity in our study was not as high as that reported with standard 3-weekly cisplatin 100 mg/m2 in other reports.,, Chemotherapy regimens with higher toxicity profiles can compromise the chemotherapy completion rate and prolong the length of RT treatment both of which can result in inferior treatment outcomes.,,,, A relatively high proportion of the patients in Group A (79%) and B (87%) tolerated chemotherapy without dose modification or discontinuation in our study. However, more severe mucositis and dermatitis in Group B (52.9%) led to a longer length of RT treatment than in Group A (46.5%). Although a prolonged RT time has been shown to be a poor prognosticator in LA-SCCHN, this factor did not affect the survival outcomes in this study.
The results of efficacy endpoints in this study, which included 1−3-year OS, PFS, and LRFS, were quite similar to other retrospective studies.,,, No additional survival benefits were observed when multiagent regimens were compared to the single-agent cisplatin in this study and other reports.,,,, However, it is still debatable as to whether the optimal dosing schedule of single-agent cisplatin acts as a radiosensitizer. Weekly cisplatin 30−40 mg/m2 and a split dose of cisplatin are the most frequently tested schedules.,, High-dose 3-weekly cisplatin may be a less tolerated regimen in head and neck cancer patients, especially in Asian populations. Regimens with weekly cisplatin alone or in combination with 5-FU have commonly been reported in this patient population to improve compliance and treatment efficacy., Due to its convenience and less toxicity, weekly cisplatin during CCRT is a frequently used regimen in Taiwan. Despite improved toxicity profiles, weekly cisplatin regimens cannot replace the standard 3-weekly cisplatin regimen from the aspect of treatment efficacy., In addition, no previous study has tested a modified 3-weekly cisplatin regimen as used in this study. Apart from the disease stage, we found that lower pretreatment Hb level (<13 g/dL) resulted in inferior survival outcomes in both the univariate and multivariate analyses. The pretreatment anemia has been reported to be a poor prognostic factor in LA-SCCHN patients in several studies.,, Anemia itself can represent an indicator of poor general condition and nutritional status before treatment. Moreover, anemia may contribute to tumor hypoxia and decrease CCRT efficacy.
Although the treatment efficacy and toxicity profile of the two regimens in our study were comparable to those reported in other studies, our results should still be interpreted with caution due to its retrospective nature. In addition, data on the human papillomavirus status of the oropharyngeal tumors (accounting for 30.6% of the overall study population) were not available in this study, although this has been shown to play a significant role in treatment response and survival outcomes.
| conclusion|| |
In summary, we demonstrated that both the modified 3-weekly cisplatin and cisplatin/5-FU regimens were well tolerated and had high treatment completion rates. However, the multiagent regimen did not enhance the treatment outcomes and increased CCRT toxicity. Based on the current evidence, 3-weekly cisplatin treatment should still be the standard regimen of care for patients undergoing CCRT for SCCHN. Further studies may be warranted to investigate dose modification of 3-weekly cisplatin.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Argiris A, Karamouzis MV, Raben D, Ferris RL. Head and neck cancer. Lancet 2008;371:1695-709.
Pignon JP, Bourhis J, Domenge C, Designé L. Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinoma: Three meta-analyses of updated individual data. MACH-NC collaborative group. Meta-analysis of chemotherapy on head and neck cancer. Lancet 2000;355:949-55.
Pignon JP, le Maître A, Maillard E, Bourhis J; MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009;92:4-14.
Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, et al.
Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350:1937-44.
Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre JL, Greiner RH, et al.
Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004;350:1945-52.
Forastiere AA, Goepfert H, Maor M, Pajak TF, Weber R, Morrison W, et al.
Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer. N Engl J Med 2003;349:2091-8.
Nguyen-Tan PF, Zhang Q, Ang KK, Weber RS, Rosenthal DI, Soulieres D, et al.
Randomized phase III trial to test accelerated versus standard fractionation in combination with concurrent cisplatin for head and neck carcinomas in the Radiation Therapy Oncology group 0129 trial: Long-term report of efficacy and toxicity. J Clin Oncol 2014;32:3858-66.
Machtay M, Moughan J, Trotti A, Garden AS, Weber RS, Cooper JS, et al.
Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: An RTOG analysis. J Clin Oncol 2008;26:3582-9.
Bauml JM, Vinnakota R, Anna Park YH, Bates SE, Fojo T, Aggarwal C, et al.
Cisplatin every 3 weeks versus weekly with definitive concurrent radiotherapy for squamous cell carcinoma of the head and neck. J Natl Cancer Inst 2019;111:490-7.
Rades D, Kronemann S, Meyners T, Bohlen G, Tribius S, Kazic N, et al.
Comparison of four cisplatin-based radiochemotherapy regimens for nonmetastatic stage III/IV squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 2011;80:1037-44.
Boscolo-Rizzo P, Gava A, Marchiori C, Baggio V, Da Mosto MC. Functional organ preservation in patients with locoregionally advanced head and neck squamous cell carcinoma treated by platinum-based multidrug induction chemotherapy and concurrent chemoradiotherapy. Ann Oncol 2011;22:1894-901.
Fesneau M, Pointreau Y, Chapet S, Martin L, Pommier P, Alfonsi M, et al.
Concomitant chemoradiotherapy using carboplatin, tegafur-uracil and leucovorin for stage III and IV head-and-neck cancer: Results of GORTEC phase II study. Int J Radiat Oncol Biol Phys 2010;76:154-63.
Salama JK, Stenson KM, Kistner EO, Mittal BB, Argiris A, Witt ME, et al.
Induction chemotherapy and concurrent chemoradiotherapy for locoregionally advanced head and neck cancer: A multi-institutional phase II trial investigating three radiotherapy dose levels. Ann Oncol 2008;19:1787-94.
Adelstein DJ, Saxton JP, Rybicki LA, Esclamado RM, Wood BG, Strome M, et al.
Multiagent concurrent chemoradiotherapy for locoregionally advanced squamous cell head and neck cancer: Mature results from a single institution. J Clin Oncol 2006;24:1064-71.
Su NW, Leu YS, Lee JC, Chen YJ, Chen HW, Liu CJ, et al.
Comparison of the efficacy and toxicity of two dose levels of cisplatin/5-fluorouracil as the chemoradiotherapy regimen for the treatment of locally advanced squamous cell carcinoma of the head and neck. Acta Otolaryngol 2011;131:1333-40.
Nakano K, Sato Y, Toshiyasu T, Sato Y, Inagaki L, Tomomatsu J, et al.
Predictive factors of head and neck squamous cell carcinoma patient tolerance to high-dose cisplatin in concurrent chemoradiotherapy. Mol Clin Oncol 2016;4:303-9.
Kumar RR, Haridas G, Kainickal CT, Sudha AS, Rafi M, Raghavan R, et al
. Phase 2b randomized trialcomparing concurrent chemoradiation with weekly versus 3 weekly cisplatinum in locally advanced head and neck squamous cell carcinoma. Int J Radiat Oncol Biol Phys 2014;90:S566.
Rades D, Fehlauer F, Sheikh-Sarraf M, Kazic N, Basic H, Poorter R, et al.
Toxicity of two cisplatin-based radiochemotherapy regimens for the treatment of patients with stage III/IV head and neck cancer. Head Neck 2008;30:235-41.
Tribius S, Kronemann S, Kilic Y, Schroeder U, Hakim S, Schild SE, et al.
Radiochemotherapy including cisplatin alone versus cisplatin+5-fluorouracil for locally advanced unresectable stage IV squamous cell carcinoma of the head and neck. Strahlenther Onkol 2009;185:675-81.
Rades D, Kronemann S, Meyners T, Schild SE, Hakim SG. Acute toxicity of three versus two courses of cisplatin for radiochemotherapy of locally advanced squamous cell carcinoma of the head and neck (SCCHN): A matched pair analysis. Oral Oncol 2010;46:549-52.
Espeli V, Zucca E, Ghielmini M, Giannini O, Salatino A, Martucci F, et al.
Weekly and 3-weekly cisplatin concurrent with intensity-modulated radiotherapy in locally advanced head and neck squamous cell cancer. Oral Oncol 2012;48:266-71.
Rades D, Seidl D, Janssen S, Bajrovic A, Hakim SG, Wollenberg B, et al.
Do we need 5-FU in addition to cisplatin for chemoradiation of locally advanced head-and-neck cancer? Oral Oncol 2016;57:40-5.
Rades D, Seidl D, Janssen S, Bajrovic A, Hakim SG, Wollenberg B, et al.
Chemoradiation of locally advanced squamous cell carcinoma of the head-and-neck (LASCCHN): Is 20mg/m (2) cisplatin on five days every four weeks an alternative to 100mg/m (2) cisplatin every three weeks? Oral Oncol 2016;59:67-72.
Rades D, Seidl D, Janssen S, Bajrovic A, Karner K, Strojan P, et al.
Comparison of weekly administration of cisplatin versus three courses of cisplatin 100 mg/m (2) for definitive radiochemotherapy of locally advanced head-and-neck cancers. BMC Cancer 2016;16:437.
Rades D, Seidl D, Janssen S, Strojan P, Karner K, Bajrovic A, et al.
Comparing two lower-dose cisplatin programs for radio-chemotherapy of locally advanced head-and-neck cancers. Eur Arch Otorhinolaryngol 2017;274:1021-7.
Cannon DM, Geye HM, Hartig GK, Traynor AM, Hoang T, McCulloch TM, et al.
Increased local failure risk with prolonged radiation treatment time in head and neck cancer treated with concurrent chemotherapy. Head Neck 2014;36:1120-5.
Salama JK, Seiwert TY, Vokes EE. Chemoradiotherapy for locally advanced head and neck cancer. J Clin Oncol 2007;25:4118-26.
Geiger JL, Lazim AF, Walsh FJ, Foote RL, Moore EJ, Okuno SH, et al.
Adjuvant chemoradiation therapy with high-dose versus weekly cisplatin for resected, locally-advanced HPV/p16-positive and negative head and neck squamous cell carcinoma. Oral Oncol 2014;50:311-8.
Lu HJ, Yang CC, Wang LW, Chu PY, Tai SK, Chen MH, et al.
Modified weekly cisplatin-based chemotherapy is acceptable in postoperative concurrent chemoradiotherapy for locally advanced head and neck cancer. Biomed Res Int 2015;2015:307576.
Lee YJ, Lee CG, Cho BC, Kim GE, Choi HJ, Choi EC, et al.
Weekly 5-fluorouracil plus cisplatin for concurrent chemoradiotherapy in patients with locally advanced head and neck cancer. Head Neck 2010;32:235-43.
Tsan DL, Lin CY, Kang CJ, Huang SF, Fan KH, Liao CT, et al.
The comparison between weekly and three-weekly cisplatin delivered concurrently with radiotherapy for patients with postoperative high-risk squamous cell carcinoma of the oral cavity. Radiat Oncol 2012;7:215.
Guan J, Zhang Y, Li Q, Zhang Y, Li L, Chen M, et al.
A meta-analysis of weekly cisplatin versus three weekly cisplatin chemotherapy plus concurrent radiotherapy (CRT) for advanced head and neck cancer (HNC). Oncotarget 2016;7:70185-93.
Szturz P, Wouters K, Kiyota N, Tahara M, Prabhash K, Noronha V, et al.
Weekly low-dose versus three-weekly high-dose cisplatin for concurrent chemoradiation in locoregionally advanced non-nasopharyngeal head and neck cancer: A Systematic review and meta-analysis of aggregate data. Oncologist 2017;22:1056-66.
van de Pol SM, Doornaert PA, de Bree R, Leemans CR, Slotman BJ, Langendijk JA. The significance of anemia in squamous cell head and neck cancer treated with surgery and postoperative radiotherapy. Oral Oncol 2006;42:131-8.
Rades D, Fehlauer F, Wroblesky J, Albers D, Schild SE, Schmidt R. Prognostic factors in head-and-neck cancer patients treated with surgery followed by intensity-modulated radiotherapy (IMRT), 3D-conformal radiotherapy, or conventional radiotherapy. Oral Oncol 2007;43:535-43.
Bhide SA, Ahmed M, Rengarajan V, Powell C, Miah A, Newbold K, et al.
Anemia during sequential induction chemotherapy and chemoradiation for head and neck cancer: The impact of blood transfusion on treatment outcome. Int J Radiat Oncol Biol Phys 2009;73:391-8.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]