An analysis on the combination of chrono-chemotherapy with different speed rate and concomitant intensity-modulated radiotherapy in the treatment of locally advanced nasopharyngeal carcinoma

Abstract

Objective To evaluate the differences of toxicities, therapeutic efficacy and immune function between induction chemotherapy followed by sinusoidal chrono-modulated infusion and flat intermittent infusion of cisplatin(DDP)with intensity-modulated radiotherapy (IMRT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Methods Seventy patients with biopsy- diagnosed stages Ⅲ and ⅣB NPC (according to the 2010 UICC staging system) were treated with two-cycle induction chemotherapy before chemoradiotherapy in Guizhou Cancer Hospital. The TPF chemotherapy regimen was administered as follows: The TXT and DDP with the dose of 75 mg/m2 was carried out by bolus infusing for the first day, the 5-FU with 750 mg·m-2·d-1 was carried out by continuous intravenous pumping for the first day to fifth day(120 h). The induction chemotherapy was 21 days per cycle, for two cycles. After that all patients were randomly treated with 2-3 cycles of sinusoidal chrono-modulated infusion or flat intermittent constant rate infusion of DDP with IMRT. Using a multi-channel programmed pump, the patients were given 12 h continuous infusions of DDP (100 mg/m2) for day one, repeated every 3 weeks for 2-3 cycles. DDP was administered from 10∶00 am to 10∶00 pm. Concurrent radiotherapy regimen was administered as follows: GTVnx 69.96-73.92 Gy/33 f, PTVnx 69.96 Gy/33 f, PTVnd 69.96 Gy/33 f, PTV1 60.06 Gy/33 f, PTV2 50.96 Gy/28 f. Results The main toxicities of chemoradiotherapy in the group of sinusoidal chrono-modulated infusion were bone marrow suppression: leukocytes, and then nausea, oral mucositis and hemoglobin. The main toxicities of chemoradiotherapy in the group of flat intermittent constant rate infusion were bone marrow suppression: hemoglobin, leukocytes, and then nausea, oral mucositis. No significant differences were observed for toxicities(P>0.05). After concurrent chemoradiotherapy, the complete response rate (CR), partial response rate (PR), stable disease rate(SD), progressive disease rate (PD) and overall response rate (ORR) were 11.4%, 85.7%, 2.9%, 0 and 97.1% in the group of sinusoidal chrono-modulated infusion. The CR, PR, SD, PD, ORR in the group of flat intermittent constant rate infusion were 22.9%, 74.2%, 2.9%, 0, 97.1%, respectively. However, there was no significant differences of effect in the two Arms(P>0.05). For sinusoidal chrono-modulated infusion and flat intermittent infusion group, the 2-year overall survival(OS) were 82.9%and 94.3% respectively, the 2-year progression-free survival(PFS) were 77.1%, 91.4% respectively, and the 2-year distant metastasis free survival(DMFS) were 82.9%, 91.4% respectively. The value of CD3+ in the group of sinusoidal chrono-modulated infusion was higher than the group of flat intermittent constant rate infusion after therapy(Z=3.254, P 0.05). Conclusions No significance differences on the toxicities, therapeutic efficacy and survival were observed between the two groups, but immune function might be improved in the sinusoidal chrono-modulated infusion group. Key words: Nasopharyngeal carcinoma; Chemotherapy; Toxicities; Efficacy; Immune function