Effectiveness and safety of different amifostine regimens: Preliminary results of a phase II multicenter randomized controlled trial
Original Article

Effectiveness and safety of different amifostine regimens: Preliminary results of a phase II multicenter randomized controlled trial

Hui Chang1*, Wei Yi2*, Xiaohui Wang1*, Yalan Tao1, Xin Yang1, Chen Chen1, Wenwen Zhang1, Shu Zhou1, Songran Liu1, Xiaohui Li3, Shirong Ding1, Jing Li4, Gong Li5, Xunfan Shao6, Yimin Liu7, Weishu Song8, Yunfei Xia1

1Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou 510060, China; 2Department of Radiation Oncology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China; 3Department of Oncology, People’s Liberation Army 421 Hospital, Guangzhou 510318, China; 4Department of Oncology, the Main Guangzhou Hospital of the Guangzhou Military Region, Guangzhou 510010, China; 5Department of Oncology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510530, China; 6Department of Radiation Oncology, the Affiliated Cancer Hospital of Guangzhou Medical College, Guangzhou 510095, China; 7Department of Radiation Oncology, the Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510120, China; 8Department of Oncology, Guangdong Second People’s Hospital, Guangzhou 510317, China

*These authors contributed equally to this work.

Correspondence to: Prof. Yunfei Xia. Department of Radiation Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China. Email: xiayf1962@126.com.


Objective: The radioprotective effects of amifostine remain uncertain in patients with nasopharyngeal carcinoma (NPC), and adverse effects and cost limit generalization of its classical everyday regimen. This phase II multicenter randomized controlled trial aimed to explore whether amifostine could ameliorate the toxicities of NPC patients in the era of intensity-modulated radiotherapy (IMRT), and to compare different regimens of amifostine on effectiveness and safety.

Methods: Patients with stage I–IVB NPC were involved prospectively from January 1st, 2013. All patients received radical treatment based on IMRT. After a randomization stratified by their stage, these patients were allocated into 3 groups: the group treated without amifostine, the group treated with the everyday regimen of amifostine, and the group treated with the every-other-day regimen. The 3 groups of patients were compared on radiotherapy-related acute toxicities, treatment effects of NPC, and amifostine-related complications. This trial was registered on the clinicaltrials.gov (ID: NCT01762514).

Results: Until August 31st, 2017, totally 187 patients completed experimental intervention. Only amifostine of everyday regimen appeared to reduce the patient proportion of mucositis (79.1% vs. 96.8%, P=0.002). Hypocalcemia was less common in patients treated without amifostine than in those treated with amifostine (22.6% vs. 53.4% vs. 41.8%, P=0.002). Neither complete remission rates nor the survivals were affected by amifostine.

Conclusions: Amifostine of everyday regimen could reduce mucositis in NPC patients who received IMRT, though it also had the possibility to cause more hypocalcemia.

Keywords: Nasopharyngeal carcinoma; amifostine; intensity-modulated radiotherapy; acute toxicity

Submitted Nov 13, 2017. Accepted for publication May 07, 2018.

doi: 10.21147/j.issn.1000-9604.2018.03.03


The nasopharyngeal carcinoma (NPC) is one of the most common cancers in South China (1,2) and mainly treated through radiotherapy (RT) (3). The intensity-modulated radiotherapy (IMRT) brings a 5-year overall survival (OS) of 85.0% (4). Contrarily, there are still many patients suffering from severe RT-related toxicities. The total incidence of grade 3/4 acute toxicities during RT is as high as 33.2% (5). And late toxicities (incidence, 9.0%) remained the main adverse factors affecting life quality of the patients after RT (6). Because reducing the toxicities might help to ameliorate tolerance of RT and life quality of the long-term survivors, radioprotection has now become one of the research hotspots.

Amifostine (AMF) is one of the most frequently used radioprotectors. It has been proved in vitro that AMF could protect normal cells from deoxyribonucleic acid (DNA) damage, and simultaneously inhibit DNA repair of the cancer cells (7). A series of clinical studies have also revealed that AMF could reduce toxicities of RT in some solid tumors, such as head and neck (HN), ovarian, breast and lung cancers (8-10), without influencing the treatment effects (11). Oppositely, the radioprotective effects of AMF were not seen in some studies (12,13). Furthermore, the clinical value of AMF remains uncertain in NPC. Therefore, this phase II trial aimed to explore the protective and the adverse effects of AMF in NPC patients treated with IMRT. Additionally, the side effects and the high cost of the classical everyday regimen limit generalization of AMF (14), especially in the developing countries like China. This trial also aimed to compare the every-other-day regimen with the standard everyday regimen on effectiveness and safety.

Patients and methods

Registration and ethical information

This trial was registered on the clinicaltrials.gov (ID: NCT01762514). It was approved by the Institutional Review Boards of the participating centers. Written informed consent was obtained from all individual participants involved in this trial.

Study design and patients

This trial is a multicenter, randomized parallel controlled, unblinded phase II clinical trial. The details of design referred to the protocol on the clinicaltrials.gov. The patients were enrolled into this trial if they had: 1) diagnosis of untreated stage T1–4N0–3M0 [the 7th edition of the Union for International Cancer Control/American Joint Cancer Committee TNM staging classification (15)] NPC after the trial started (January 1st, 2013); 2) age between 18 and 75 years old; 3) Karnofsky performance score ≥60; and 4) expected survival time ≥3 months. The exclusion criteria included: 1) prior history of alcohol or drug abuse; 2) pregnant or lactating women; 3) treatment with other radioprotective drugs currently; 4) regular application of anti-hypertension drugs; 5) severe hypocalcemia; 6) heart, lung, liver, kidney or hematopoietic dysfunctions unsuitable for RT; 7) severe neurological, mental or endocrine diseases; 8) prior allergic reactions to AMF; or 9) participation in clinical trials of other drugs within 3 months.


A randomization stratified by stage was applied centrally in this trial, to allocate the patients into the control group (Group A), the every-other-day AMF group (Group B), and the everyday AMF group (Group C), at a ratio of 1:1:1. The allocation was unblinded for the researchers and the patients. The procedure of the randomization is summarized in Figure 1.

Figure 1 Procedure of randomization. NPC, nasopharyngeal carcinoma; KPS, Karnofsky performance score; RT, radiotherapy; CRT, chemoradiotherapy; AMF, amifostine.

Cancer treatment

The treatment strategies of all the patients were decided according to the guidelines of the National Comprehensive Cancer Network and our hospital, which was the sponsor center. Stage I–II disease was treated with RT alone, and stage III–IVB disease was treated with RT plus concurrent chemotherapy (CCT). The RT technique for all the patients was IMRT. The CCT was performed uniformly with the nedaplatin plus 5-flurouracil regimen.

AMF administration

The patients in Group A were planned to receive only the cancer treatment (RT plus CCT or not). The patients in Group B were planned to receive the cancer treatment plus AMF of every-other-day regimen (400 mg on Day 1, 3 and 5, every week for totally 6–7 weeks). And the patients in Group C were planned to receive the cancer treatment plus AMF of everyday regimen (400 mg on Day 1–5, every week for totally 6–7 weeks).

Study measurements

Before treatment, all the patients underwent a series examinations assessing baseline clinical profiles, including naspharyngoscope, physical examination (PE) and magnetic resonance imaging (MRI) of HN, thoraco-abdominal computed tomography (CT), and whole-body bone scan (or positron emission tomography).

When the RT was performed 10, 20 and 30 fractions, HN CT and nasopharyngoscope were performed for each patient to evaluate the regression of the primary tumor. The regression grade was determined based on the Response Evaluation Criteria in Solid Tumors version 1.1 (16).

HN PE, complete blood count and serum biochemistry profile were assessed once a week during RT and a week after RT. The RT-related toxicities and the AMF-related complications were decided on basis of Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (17).

The follow-up of disease status was made through outpatient interview every 3 months for the first 3 years after treatment. In the 4th and 5th years, the patients were followed up by outpatient interview or telephone semi-annually. And the patients were followed up annually thereafter, until death from NPC or August 31st, 2017, whichever came first.


The primary endpoints of this trial were: 1) proportions of patients with the most common RT-related acute toxicities of NPC (myelosuppression, xerostomia and mucositis); and 2) OS, which was defined as the percentage of patients who survived after a certain time period from pathological diagnosis (the survival patients and those lost to follow-up were regarded censored).

The secondary endpoints included: 1) proportions of patients with the grade 3/4 acute toxicities mentioned above; 2) complete remission (CR) rates at 30 fractions of RT and 3 months after RT; 3) disease-free survival (DFS), which was defined as the percentage of patients who had no death, local recurrence or distant metastasis after a certain time period from pathological diagnosis (the patients without these events and those lost to follow-up were regarded censored); and 4) proportions of patients with the most common AMF-related complications, including upper gastrointestinal (GI) reactions, hypotension and hypocalcemia.

Statistical analysis

The baseline clinical profiles, patient proportions, and CR rates among the 3 groups were compared by a Chi-square test. The survivals were calculated through the Kaplan-Meier approach, in which a log-rank test is performed to assess the differences among the 3 groups. If a statistical significance is attained, multiple comparisons between any 2 of the 3 groups will be performed.

All statistical analyses were done by IBM SPSS software (Version 23.0; IBM Corp., New York, USA). A difference with a two-sided P value of less than 0.05 was considered to be statistically significant. But for the multiple comparisons, the P value threshold was adjusted as 0.017 according to the Bonferroni correction (18).


Baseline characteristics

Until August 31st, 2017, a total of 189 patients were enrolled. Of those, 2 patients (1 case in the Group B and 1 case in the Group C) quitted the trial before RT, according to the will of the patients. Finally, 187 patients (98.9%) completed experimental intervention and were eligible for analysis. The median age of these patients was 46 (range, 18–75) years old. The numbers of the patients with stage I–II disease and those with stage III–IVB disease were 51 (27.3%) and 136 (72.7%), respectively. There were 62 (33.2%), 58 (31.0%) and 67 (35.8%) patients in the Groups A, B and C respectively. Baseline characteristics were balanced among the 3 groups (Table 1).

Table 1
Table 1 Baseline profiles, treatment effects and complications (N=187)
Full table

Protective effects of AMF

The proportions of patients with mucositis were 96.8%, 94.8% and 79.1% in the Groups A, B and C (P=0.001), respectively (Table 1). The proportions of patients with xerostomia were 87.1%, 89.7% and 86.6% (P=0.858), respectively. And the figures of myelosuppression were 66.1%, 70.7% and 64.2% (P=0.735), respectively. Multiple comparison showed that the Group C had less patients with mucositis than the Groups B and A (P=0.011 and 0.002, respectively) (Figure 2). The Groups A and B had similar patients with mucositis (P=0.594). Nevertheless, there was no difference in proportions of patients with grade 3/4 mucositis, myelosuppression or xerostomia among the 3 groups (P=0.444, 0.561 and 0.958, respectively) (Table 1, Supplementary Figure S1).

Figure 2 Multiple comparison in mucositis, xerostomia and myelosuppression. *, P<0.05; **, P<0.01.
Figure S1 Multiple comparison in grade 3/4 mucositis, xerostomia and myelosuppression. There was no statistically significant difference in proportions of patients with grade 3/4 mucositis, xerostomia or myelosuppression among the 3 groups.

Treatment results

No difference was seen in CR rates among the 3 groups at 30 fractions of RT, or 3 months after RT (P=0.279 and 0.974, respectively). After a median follow-up time of 41 (range, 6–56) months, 14 out of 187 patients (7.5%) were lost to follow-up. There was no difference either in the OS or in the DFS among the 3 groups (P=0.354 and 0.448, respectively) (Figure 3).

Figure 3 Survival curves of the 3 groups of patients. (A) Overall survival (OS). The OS of the Groups A, B and C were 98.4%, 94.8% and 98.5%, respectively (P=0.354); (B) Disease-free survival (DFS). The DFS of the Groups A, B and C were 96.8%, 91.4% and 94.0%, respectively (P=0.448).

AMF-related complications

Hypocalcemia was less common in the Group A than in the Groups B and C (P=0.002). But there was no difference in patient proportion of GI reactions or hypotension among the 3 groups (P=0.321 and 0.222, respectively) (Table 1). Further multiple comparison showed that the Group B had more patients with hypocalcemia than the Group A (53.4% vs. 22.6%, P<0.001). No difference was shown between the Group C and the Group B, or between the Group C and the Group A (P=0.193 and 0.020, respectively) (Supplementary Figure S2).

Figure S2 Multiple comparison in gastrointestinal (GI) reactions, hypotension and hypocalcemia. **, P<0.01.


AMF of the everyday regimen (400 mg/d, 5 d per week) concurrently with RT was proved in this trial to decrease the patient proportion of mucositis, compared with RT alone (79.1% vs. 96.8%, P=0.002). The result was reliable because the trial was a multicenter randomized controlled trial enrolling relatively large scale of NPC patients. For NPC, there was no such strong evidence before. Considering mucositis has been reported as the most common acute toxicity (incidence, 99.0%–99.4%) during RT (5,19), AMF might help to improve RT tolerance of NPC patients. Additionally, a recent study by You et al. indicated that combining chemotherapy with agents targeting epidermal growth factor receptor could further elevate the survival of locally advanced NPC, as well as the risk of mucositis (20). It conferred broader prospect of application to AMF. However, in this trial, the proportion of patients with grade 3/4 mucositis was not influenced by AMF.

Prior to our study, there were a series of approaches which also showed radioprotective effects of AMF in HN cancers. A study by Münter et al. indicated that AMF could relieve decline in excretion rate of salivary glands after RT (21). Büntzel et al. also showed in a prospective cohort study involving 851 patients that AMF could ameliorate late xerostomia and altered taste significantly (22). Furthermore, Gu et al. made a meta-analysis summarizing 17 trials until January 2012 to demonstrate that AMF could decrease the risk of developing grade 3/4 acute mucositis, xerostomia and dysphagia (23). In addition, a study by Saavedra et al. revealed that AMF had a potential to alter radio-induced apoptosis of peripheral blood cells (24).

Yet, evidences on application of AMF are unconsistent. In a phase II randomized controlled trial of Haddad et al., AMF did not bring improvement of acute xerostomia or mucositis to patients who received chemoradiotherapy (25). The protective effects of AMF on acute or late xerostomia were not seen in a systemic review by Riley et al., either (14). In our study, neither myelosuppression nor xerostomia was reduced when AMF was administrated. Therefore, more evidences are needed to validate the radioprotection from AMF, particularly the strong evidences from randomized controlled trials.

AMF itself could also cause some complications. The most common grade 3/4 side effects of AMF are hypocalcemia, emesis, nausea, hypotension and allergic reactions (incidences were 8.6%, 6.0%, 5.0%, 4.0% and 4.0%, respectively) (23,26). Some rare complications such as Stevens-Johnson syndrome and toxic epidermal necrolysis were also reported (27). In our study, AMF did not increase incidence of GI reactions or hypotension. Nevertheless, compared with RT alone, concomitant AMF of every-other-day regimen presented to cause more hypocalcemia (53.4% vs. 22.6%, P<0.001). And though statistical significance was not achieved, the everyday regimen still had a potential possibility to increase hypocalcemia (41.8% vs. 22.6%, P=0.020). Additionally, subcutaneous injection of AMF was reported to cause fewer complications than intravenous injection. Meanwhile, the protective effects of the former might be weaker as well (23,28). Admittedly, it is another concern whether AMF influences the treatment effects of RT. Our study showed that neither CR rates (at 30 fractions of RT or at 3 months after RT) nor the survivals (OS or DFS) were affected by AMF. These results were in accordance with the previous studies performed in HN and lung cancers (11). Hence, AMF was a safe choice for radioprotection of NPC patients.

Indeed, there were some limitations in our study. First, it was not done in a double-blind manner because enough financial and technical support was lacked. Second, late toxicities were not compared among patients with different regimens of AMF. It was because that this trial focused mainly on the acute toxicities, which were the main factors affecting the RT tolerance. Last, the follow-up time was relatively short for NPC, which had an ideal long-term outcome. The follow-up will be continued to report more exact results of prognosis.


AMF of everyday regimen appeared to reduce mucositis in NPC patients who received IMRT, though it also had the possibility to bring more hypocalcemia. And we still recommended that the results of our study be further verified by a phase III trial with a longer follow-up before generalization.


We are grateful to Prof. Qing Liu (Department of Preventive Medicine, Sun Yat-sen University Cancer Center) for his technical help in the statistical procedure. This study was supported by the grants of the Hi-Tech Research and Development Program of China (Grant No. 2006AA02Z4B4) and the National Key Projects of Research and Development of China (Grant No. 2016YFC0904600). The funding sources had no role in the study design, data collection, analysis, interpretation or writing of the manuscript.


Conflicts of Interest: The authors have no conflicts of interests to declare.


  1. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin 2016;66:115–32. [PubMed] DOI:10.3322/caac.21338
  2. Meng R, Wei K, Xia L, et al. Cancer incidence and mortality in Guangdong province, 2012. Chin J Cancer Res 2016;28:311–20. [PubMed] DOI:10.21147/j.issn.1000-9604.2016.03.05
  3. Chua MLK, Wee JTS, Hui EP, et al. Nasopharyngeal carcinoma. Lancet 2016;387:1012–24. [PubMed] DOI:10.1016/S0140-6736(15)00055-0
  4. Lee AW, Ng WT, Chan LL, et al. Evolution of treatment for nasopharyngeal cancer — success and setback in the intensity-modulated radiotherapy era. Radiother Oncol 2014;110:377–84. [PubMed] DOI:10.1016/j.radonc.2014.02.003
  5. Li G, Jiang XY, Qiu B, et al. Vicious circle of acute radiation toxicities and weight loss predicts poor prognosis for nasopharyngeal carcinoma patients receiving intensity modulated radiotherapy. J Cancer 2017;8:832–8. [PubMed] DOI:10.7150/jca.17458
  6. Huang TL, Chien CY, Tsai WL, et al. Long-term late toxicities and quality of life for survivors of nasopharyngeal carcinoma treated with intensity-modulated radiotherapy versus non-intensity-modulated radiotherapy. Head Neck 2016;38 Suppl 1:E1026–32. [PubMed] DOI:10.1002/hed.24150
  7. Hofer M, Falk M, Komůrková D, et al. Two new faces of amifostine: Protector from DNA damage in normal cells and inhibitor of DNA repair in cancer cells. J Med Chem 2016;59:3003–17. [PubMed] DOI:10.1021/acs.jmedchem.5b01628
  8. Brizel DM, Overgaard J. Does amifostine have a role in chemoradiation treatment?. Lancet Oncol 2003;4:378–81. [PubMed] DOI:10.1016/S1470-2045(03)01132-X
  9. Koukourakis MI, Panteliadou M, Abatzoglou IM, et al. Postmastectomy hypofractionated and accelerated radiation therapy with (and without) subcutaneous amifostine cytoprotection. Int J Radiat Oncol Biol Phys 2013;85:e7–13. [PubMed] DOI:10.1016/j.ijrobp.2012.08.017
  10. Devine A, Marignol L. Potential of amifostine for chemoradiotherapy and radiotherapy-associated toxicity reduction in advanced NSCLC: A meta-analysis. Anticancer Res 2016;36:5–12. [PubMed]
  11. Bourhis J, Blanchard P, Maillard E, et al. Effect of amifostine on survival among patients treated with radiotherapy: a meta-analysis of individual patient data. J Clin Oncol 2011;29:2590–7. [PubMed] DOI:10.1200/JCO.2010.33.1454
  12. Nicolatou-Galitis O, Sarri T, Bowen J, et al. Systematic review of amifostine for the management of oral mucositis in cancer patients. Support Care Cancer 2013;21:357–64. [PubMed] DOI:10.1007/s00520-012-1613-6
  13. Lawrence YR, Paulus R, Langer C, et al. The addition of amifostine to carboplatin and paclitaxel based chemoradiation in locally advanced non-small cell lung cancer: long-term follow-up of Radiation Therapy Oncology Group (RTOG) randomized trial 9801. Lung Cancer 2013;80:298–305. [PubMed] DOI:10.1016/j.lungcan.2013.02.008
  14. Riley P, Glenny AM, Hua F, et al Pharmacological interventions for preventing dry mouth and salivary gland dysfunction following radiotherapy. Pharmacological interventions for preventing dry mouth and salivary gland dysfunction following radiotherapy. Cochrane Database Syst Rev 2017;7:CD012744. [PubMed] DOI:10.1002/14651858.CD012744
  15. OuYang PY, Su Z, Ma XH, et al. Comparison of TNM staging systems for nasopharyngeal carcinoma, and proposal of a new staging system. Br J Cancer 2013;109:2987–97. [PubMed] DOI:10.1038/bjc.2013.659
  16. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228–47. [PubMed] DOI:10.1016/j.ejca.2008.10.026
  17. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 (June 14, 2010). U. S. Department of Health and Human Services, National Cancer Institute, National Institutes of Health. Available online: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf
  18. Logan BR, Wang H, Zhang MJ. Pairwise 'multiple comparison adjustment in survival analysis. Stat Med 2005;24:2509–23. [PubMed] DOI:10.1002/sim.2125
  19. Lin L, Yao JJ, Zhou GQ, et al. The efficacy and toxicity of individualized intensity-modulated radiotherapy based on the tumor extension patterns of nasopharyngeal carcinoma. Oncotarget 2016;7:20680–90. [PubMed] DOI:10.18632/oncotarget.8004
  20. You R, Hua YJ, Liu YP, et al. Concurrent chemoradiotherapy with or without Anti-EGFR-targeted treatment for stage II–IVb nasopharyngeal carcinoma: Retrospective analysis with a large cohort and long follow-up. Theranostics 2017;7:2314–24. [PubMed] DOI:10.7150/thno.19710
  21. Münter MW, Hoffner S, Hof H, et al. Changes in salivary gland function after radiotherapy of head and neck tumors measured by quantitative pertechnetate scintigraphy: comparison of intensity-modulated radiotherapy and conventional radiation therapy with and without Amifostine. Int J Radiat Oncol Biol Phys 2007;67:651–9. [PubMed] DOI:10.1016/j.ijrobp.2006.09.035
  22. Büntzel J, Glatzel M, Mücke R, et al. Influence of amifostine on late radiation-toxicity in head and neck cancer — a follow-up study. Anticancer Res 2007;27:1953–6. [PubMed]
  23. Gu J, Zhu S, Li X, et al. Effect of amifostine in head and neck cancer patients treated with radiotherapy: a systematic review and meta-analysis based on randomized controlled trials. PLoS One 2014;9:e95968. [PubMed] DOI:10.1371/journal.pone.0095968
  24. Saavedra MM, Henríquez-Hernández LA, Lara PC, et al. Amifostine modulates radio-induced apoptosis of peripheral blood lymphocytes in head and neck cancer patients. J Radiat Res 2010;51:603–7. [PubMed] DOI:10.1269/jrr.10030
  25. Haddad R, Sonis S, Posner M, et al. Randomized phase 2 study of concomitant chemoradiotherapy using weekly carboplatin/paclitaxel with or without daily subcutaneous amifostine in patients with locally advanced head and neck cancer. Cancer 2009;115:4514–23. [PubMed] DOI:10.1002/cncr.24525
  26. Souid AK, Dubowy RL, Blaney SM, et al. Phase I clinical and pharmacologic study of weekly cisplatin and irinotecan combined with amifostine for refractory solid tumors. Clin Cancer Res 2003;9:703–10. [PubMed]
  27. Valeyrie-Allanore L, Poulalhon N, Fagot JP, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis induced by amifostine during head and neck radiotherapy. Radiother Oncol 2008;87:300–3. [PubMed] DOI:10.1016/j.radonc.2008.01.021
  28. Bardet E, Martin L, Calais G, et al. Subcutaneous compared with intravenous administration of amifostine in patients with head and neck cancer receiving radiotherapy: final results of the GORTEC2000-02 phase III randomized trial. J Clin Oncol 2011;29:127–33. [PubMed] DOI:10.1200/JCO.2009.25.5638
  29. Cite this article as: Chang H, Yi W, Wang X, Tao Y, Yang X, Chen C, Zhang W, Zhou S, Liu S, Li X, Ding S, Li J, Li G, Shao X, Liu Y, Song W, Xia Y. Effectiveness and safety of different amifostine regimens: Preliminary results of a phase II multicenter randomized controlled trial. Chin J Cancer Res 2018;30(3):307-314. doi: 10.21147/j.issn.1000-9604.2018.03.03