Outpatient weekly 24-hour infusional adjuvant chemotherapy of cisplatin, 5-fluorouracil, and leucovorin for high-risk nasopharyngeal carcinoma.

Distant metastasis rather than locoregional recurrence is the major site of failure after adequate radiotherapy in nasopharyngeal carcinoma (NPC). The aim of this study is to evaluate the toxicity and survival of outpatient weekly 24-hour infusion adjuvant chemotherapy for NPC patients with high-risk of distant failure. Our definition of high-risk NPC included patients with (1) 1992 AJCC staging system of N3, T4N2, or N2 with one of nodal size > 4 cm; (2) supraclavicular node metastasis; and (3) residual disease after radiotherapy or neck relapse. From August 1994 to August 1997, 41 NPC patients matching the preceding criteria agreed to receive weekly PFL (cisplatin 25 mg/m(2), 5-fluorouracil 1250 mg/m(2), and leucovorin 120 mg/m(2)) adjuvant chemotherapy for a total of 18 weeks. Clinical data of another 88 patients with similar disease status who did not receive adjuvant chemotherapy during the same period were collected and analyzed for comparison. Survival analysis was investigated by the Kaplan-Meier method and the Cox proportional hazards model. A total of 700 weekly chemotherapy doses was delivered to 41 patients. The ratio of actual/planned dose delivery was 94.9%. Grade 3-4 toxicity of adjuvant chemotherapy included leucopenia (7.3%), anemia (2.4%), thrombocytopenia (2.4%), and nausea/vomiting (2.4%). After a median follow-up of 70 months, 26.8% (11 of 41) and 47.7% (42 of 88) of patients in PFL and no adjuvant chemotherapy groups had distant metastasis (p =.0247). The 5-year metastasis-free survival rates were 71.9% for the PFL group compared with 48.4% for no adjuvant chemotherapy patients (p =.0187). The 5-year overall survival rates were 53.7% (PFL group) and 38.3% (no adjuvant chemotherapy group), respectively (p =.0666). Multivariate Cox analysis showed PFL adjuvant chemotherapy was the independent factor that predicted metastasis-free survival after adjustment for other variables. Outpatient weekly 24-hour continuous infusion PFL adjuvant chemotherapy is a well-tolerated regimen with promising results in high-risk NPC patients and merits investigation in phase III studies.

Lin JC ，Jan JS ，Chen KY ，Hsu CY ，Liang WM ，Wang WY ... -  《HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK》

Outpatient weekly neoadjuvant chemotherapy followed by radiotherapy for advanced nasopharyngeal carcinoma: high complete response and low toxicity rates.

Lin JC ，Jan JS ，Hsu CY ，Jiang RS ，Wang WY ... -  《-》

Adjuvant fractionated high-dose-rate intracavitary brachytherapy after external beam radiotherapy in Tl and T2 nasopharyngeal carcinoma.

The value of high-dose-rate intracavitary brachytherapy (HDRIB) for persistent or recurrent nasopharyngeal carcinoma has been well described; however, the benefit of routine adjuvant fractionated HDRIB following external beam radiation therapy (EBRT) has not been completely determined. The objective of this analysis was to evaluate the outcome of two fractions of adjuvant HDRIB treatment in Tl and T2 nasopharyngeal carcinoma. Thirty-three consecutive and nonselected patients who had Tl and T2 non-disseminated nasopharyngeal carcinoma were treated according to an IRB approved institutional research protocol between March 1999 and July 2001. By the 1997 AJCC cancer staging classification, 22 patients (67%) had Tl disease and 11 patients (33%) had T2 disease. Seventeen of these patients who had stage I or stage II disease (i.e., NO or Nl) were treated with EBRT followed by two fractions of adjuvant HDRIB (group 1); 16 patients who had stage III or stage IV disease (i.e., N2 or N3) were treated with concurrent cisplatin, EBRT and adjuvant HDRIB and subsequent adjuvant cisplatin and fluorouracil (5-FU) chemotherapy (group 2). EBRT was delivered by daily conventional fractionation to a total dose of 66 Gy to the primary tumor. Nodal disease received 66 Gy if it was less than 3 cm in maximum diameter and 70 Gy if larger or there was palpable residual disease after 66 Gy. A total of 10 Gy of HDRIB in 2 equal fractions of 5 Gy spaced 1 week apart was delivered starting 1 week after the completion of EBRT. All patients were assessed for treatment response, local control, survival, and toxicity. The median follow up for all 29 surviving patients is 29 months (range: 17-38 months). One patient died 7 months and one died 18 months after radiation therapy from the effects of distant metastases; two died of unrelated causes. At the time of this analysis, one patient (3%) had persistent local disease and one patient (3%) developed pathologically confirmed local recurrence in the nasopharynx. In addition, one patient (3%) developed recurrence only in a neck node followed by distant metastasis, and two patients (6%) developed distant metastasis without locoregional relapse. The 2-year local control rate at the primary site was 93.6%, and the overall survival and disease-free survival rates were 82% and 74% respectively. All patients experienced some degree of acute and/or late toxicity related to radiation therapy. Ten patients (30%) experienced grade 3 acute and/or late toxicity and six patients (18%) developed grade 4 acute and/or late toxicity. No grade 5 toxicity occurred. No unexpected damage of structures within the HDRIB fields was detected. EBRT supplemented by two fractions of adjuvant HDRIB produced a 93.6% local control rate for Tl and T2 nasopharyngeal cancer at 2 years of follow up, with acceptable rates of acute and late toxicity. Brief adjuvant HDRIB appears to permit dose escalation safely, even in patients who receive chemotherapy concurrently with conventional radiation therapy. This strategy needs to be optimized and then tested in a prospective randomized phase III trial to learn if it can improve outcome.

Lu JJ ，Shakespeare TP ，Tan LK ，Goh BC ，Cooper JS ... -  《HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK》

A concurrent chemoirradiation with cisplatin followed by adjuvant chemotherapy with ifosfamide, 5-fluorouracil, and leucovorin for stage IV nasopharyngeal carcinoma.

To evaluate the toxicity and efficacy of concurrent chemoirradiation with cisplatin followed by adjuvant ifosfamide, 5-fluorouracil and leucovorin in patients with stage IVb nasopharyngeal carcinoma (NPC) PATIENTS AND METHODS: Between October 1998 and August 2001, 35 Chinese patients with stage IVb NPC (N3a:12, N3b:23) were treated with by concurrent chemoirradiation using cisplatin 100 mg/m2 on days 1, 22, and 43 of radiotherapy, followed by adjuvant chemotherapy with 1.4 g/m2, ifosfamide, 450 mg/m2 5-fluorouracil, and 20 mg/m2 leucovorin daily for 5 days and repeated every 3 weeks for three cycles. Radiotherapy was given using standard fractionation at 2 Gy/day to a total of 68 Gy to the nasopharynx and 66 Gy to the neck. All patients completed the prescribed radiotherapy. Twenty-three patients (66%) completed all scheduled cycles of chemotherapy. The compliance rate for concurrent and adjuvant chemotherapy was 71% and 80%, respectively. Grade 3 mucositis occurred in 37%, and grade 3 dermatitis occurred in 11.5% during radiotherapy. Grade 3 neutropenia occurred in 17% during concurrent chemotherapy, and grade 3-4 neutropenia occurred in 48.5% during adjuvant chemotherapy. There were no treatment-related deaths. With a median follow-up of 31 months, the 3-year relapse-free rate was 60%, and the 3-year overall survival rate was 74%. Locoregional control was excellent, with a 3-year local and nodal relapse-free rate of 91% and 83%, respectively. Eleven patients (31%) had developed distant metastases, and the 3-year distant metastasis-free rate was 66%. The chemotherapy regimen tested is practical with an acceptable compliance rate. Despite having a more advanced stage disease, the observed outcome of our patients seems to be comparable with other series using platinum-based adjuvant chemotherapy. Further investigation to confirm the benefit of using the study regimen in advanced stage NPC is warranted.

Chua DT ，Sham JS ，Au GK 《HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK》

Induction with mitomycin C, doxorubicin, cisplatin and maintenance with weekly 5-fluorouracil, leucovorin for treatment of metastatic nasopharyngeal carcinoma: a phase II study.

Hong RL ，Sheen TS ，Ko JY ，Hsu MM ，Wang CC ，Ting LL ... -  《-》