Abitbol A A, Sridhar K S, Lewin A A, Schwade J G, Raub W, Wolfson A, Gonzalez-Angulo C, Adessa A, Goodwin W J, Markoe A M
Department of Radiation Oncology, Sylvester Cancer Center, University of Miami School of Medicine, Florida, USA.
Cancer. 1997 Jul 15;80(2):266-76. doi: 10.1002/(sici)1097-0142(19970715)80:2<266::aid-cncr15>3.0.co;2-s.
The authors had previously reported preliminary results of a treatment regimen of concurrent hyperfractionated radiation therapy and chemotherapy in patients with locally advanced head and neck carcinoma that demonstrated both feasibility and high local control. In an attempt to reduce acute mucosal and hematologic toxicity, granulocyte-colony stimulating factor (G-CSF) was added during the second phase of this study.
Seventy patients (53 with Stage IV and 17 with Stage III disease) were entered between May 1988 and June 1995 into a Phase I/II trial of concurrent radiation therapy (74.4 gray (Gy) total dose; 1.20 Gy twice daily), 5-fluorouracil (1000 mg/m2/24 hours for 72 hours), and cisplatin (50 mg/m2) for 3 cycles with the addition of mitomycin C (8 mg/m2) in Cycle 2. G-CSF was added after the initial entry of 34 patients.
At a median follow-up of 41 months (range, 12-80 months), 44 patients were alive with a projected median overall survival of 54 months. Grade 3/4 mucositis, observed in 65% of patients, was equally prevalent and prolonged in both G-CSF-treated (+) and G-CSF-naive (-) patients. Grade 3/4 leukopenia was present in 45% and 36% of G-CSF- and G-CSF+ patients, respectively. The 3-year locoregional control and cause specific survival rates were 68% and 75%, respectively.
This regimen was feasible and effective but caused severe mucositis. No benefit was derived from the addition of G-CSF. This regimen deserves further modification to reduce acute mucositis toxicity yet maintain the high locoregional control rate.
作者之前曾报道过局部晚期头颈癌患者同步超分割放疗与化疗治疗方案的初步结果，该方案显示出可行性和较高的局部控制率。为了降低急性黏膜和血液学毒性，在本研究的第二阶段加入了粒细胞集落刺激因子（G-CSF）。
1988年5月至1995年6月期间，70例患者（53例IV期和17例III期疾病患者）进入了一项I/II期试验，接受同步放疗（总剂量74.4格雷（Gy）；每日两次，每次1.20 Gy）、5-氟尿嘧啶（1000 mg/m²/24小时，共72小时）和顺铂（50 mg/m²），共3个周期，第2周期加用丝裂霉素C（8 mg/m²）。在最初的34例患者入组后加入G-CSF。
中位随访41个月（范围12 - 80个月）时，44例患者存活，预计中位总生存期为54个月。65%的患者出现3/4级黏膜炎，在接受G-CSF治疗（+）和未接受G-CSF治疗（-）的患者中同样普遍且持续时间相同。3/4级白细胞减少分别出现在45%的G-CSF-患者和36%的G-CSF+患者中。3年局部区域控制率和病因特异性生存率分别为68%和75%。
该方案可行且有效，但会导致严重的黏膜炎。加入G-CSF未带来益处。该方案值得进一步改进，以降低急性黏膜炎毒性，同时维持较高的局部区域控制率。
