Sequential methotrexate, 5-fluorouracil, and calcium leucovorin in colorectal carcinoma

Forty-four patients with locally recurrent or metastatic colorectal adenocarcinoma were treated with methotrexate (MTX) 100 mg/m2 i.v. followed 1 h later by 5-fluorouracil (5-FU) 600 mg/m2 i.v. Calcium leucovorin 10 mg/m2 p.o. q 6 h X four doses was given 24 h after MTX. The regimen was given on days 1 and 8 and repeated every 28 days. Six of 44 patients (14%) obtained either complete or partial response with a mean response duration of 6.8 months. Of 26 previously untreated patients there were one complete response (4%), four partial responses (15%), and 12 (46%) instances of stabilization of disease. Patients obtaining response or stabilization of disease experienced improved survival compared to those with progressive disease. Toxicity consisted of stomatitis and hematopoietic suppression requiring dose attenuation in six patients (14%); there were no treatment-related deaths. Sequenced MTX/5-FU is modestly active with acceptable toxicity in previously untreated patients with colorectal adenocarcinoma but offers no apparent advantage over single-agent 5-FU.     

Experience with combination of docetaxel, cisplatin plus 5-fluorouracil chemotherapy, and intensity-modulated radiotherapy for locoregionally advanced nasopharyngeal carcinoma

Background

Our aim was to evaluate the efficacy and toxicity of cisplatin, fluorouracil, and docetaxel chemotherapy plus intensity-modulated radiotherapy (IMRT) for locoregionally advanced nasopharyngeal carcinoma (NPC).

Methods

Sixty patients with locoregionally advanced NPC were enrolled. Patients received IMRT plus three courses of neoadjuvant chemotherapy and two courses of adjuvant chemotherapy consisting of docetaxel (60 mg/m²/day on day 1), cisplatin (25 mg/m²/day on days 1–3), and 5-fluorouracil (500 mg/m²/day on days 1–3).

Results

The overall response rate to neoadjuvant chemotherapy was 89 %. Three months after the completion of radiotherapy, 53 (93 %) patients achieved complete regression, 3 (5 %) achieved partial response (PR), and 1 experienced liver metastasis. However, among the 3 PR patients, 2 patients had no evidence of relapse in the follow-up. With a median follow-up of 27 months (range, 6–43), the 2-year estimated locoregional failure-free survival, distant failure-free survival, progression-free survival, and overall survival were 96.6, 93.3, 89.9, and 98.3 %, respectively. Leukopenia was the main adverse effect in chemotherapy; 14 patients experienced grade 3 or grade 4 neutropenia, and 1 patient developed febrile neutropenia. The nonhematological adverse events included alopecia, nausea, vomiting, anorexia, and diarrhea. The incidence of grade 3 acute radiotherapy-related mucositis was 28.3 %; no grade 4 acute mucositis was observed. No grade 3 or grade 4 hematological toxicity occurred during radiotherapy. None of the patients had interrupted radiotherapy. The common late adverse effects included xerostomia and hearing impairment.

Conclusions

Neoadjuvant–adjuvant chemotherapy using cisplatin, fluorouracil, plus docetaxel combined with IMRT was an effective and well-tolerated alternative for advanced NPC.     

Chemotherapy with etoposide,doxorubicin, cisplatin, 5-fluorouracil,and leucovorin for patients with advanced hepatocellular carcinoma

BACKGROUND: To investigate the therapeutic index of combining etoposide, doxorubicin (adriamycin), cisplatin, 5-fluorouracil (5-FU), and leucovorin (EAPFL) chemotherapy in the treatment of advanced HCC, a trial of a novel schedule of triweekly administration was conducted. PATIENTS AND METHODS: Sixty-six patients with measurable advanced HCC, adequate liver and renal functions and adequate bone marrow reserves in whom local treatment was not indicated were studied. Triweekly EAPFL treatment consisted of a concomitant boost of etoposide 40 mg/m2 i.v. over 30 min on day 1, 2, and 3, doxorubicin 30 mg/m2 i.v. over 30 min on day 1 to a backbone regimen, triweekly PFL chemotherapy with cisplatin 60 mg/m2, 5-FU 1,200 mg/m2, and leucovorin 120 mg/m2 given simultaneously by a 72-h i.v. infusion. Response, survival, and toxicity were evaluated. RESULTS: One patient had complete response (1%) and thirteen patients had partial response (20%). The objective response rate was 21% (95% confidence interval 11-31%). The median overall survival and median time to progression were 8.9 months and 3.3 months, respectively. Major treatment toxicities (grade 3-4) were neutropenia (28%), anemia (11%), thrombocytopenia (7%), hepatotoxicity (5%), vomiting (2%), and diarrhea (2%). There was no treatment-related death. CONCLUSION: Triweekly EAPFL chemotherapy is a moderately effective regimen with tolerable toxicities in the treatment of advanced HCC.     

Biologic modulation of 5-fluorouracil with high-dose leucovorin and combination chemotherapy of 5-fluorouracil and cisplatin in metastatic colorectal adenocarcinoma

The data from an ongoing 3-arm prospective study of 72 patients with advanced colorectal carcinoma is presented. The 3 regimens are as follows: Regime 1 (every 4 weeks)--5-fluorouracil (FUra) (450 mg/m2 iv bolus daily for 5 days, then 200 mg/m2 iv bolus every other day for 6 doses); regime 2 (every week for 4 weeks, then every other week)--methotrexate (MTX) (50 mg/m2 in a 4-hour infusion) followed by FUra (600 mg/m2 iv bolus); regime 3 (weekly for 6 weeks followed by a 2-week rest period)--D,L-leucovorin (D,L-CF) (500 mg/m2 in a 2-hour infusion) with FUra (600 mg/m2 iv bolus) 1 hour after the D,L-CF infusion began. All monitoring lesions except lung were documented by tissue biopsy. Thirteen of 18 patients in the FUra + D,L-CF arm were evaluable for response. Six of the 13 patients (46%) have had a partial response. The duration of the 6 responses has been 11, 8, 7, 4, 3 and 3 months. In patients with liver metastases as the monitoring lesion, a dramatic improvement in liver function tests has been seen during the first 2 courses (12 weeks) of treatment, but this was not sustained. The toxicity of FUra + D,L-CF was predominantly gastrointestinal; unlike with FUra alone, myelosuppression was not predominant.     

Primary chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil in operable breast carcinoma

BACKGROUND: Primary chemotherapy (PC) is becoming an accepted practice to treat large tumors to avoid mastectomies and as a surrogate of outcome. METHODS: A series of 305 patients with tumors >3 cm with T2-3N0-1M0 classification were treated with a multimodal approach that consisted of 3 courses of primary cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) followed by appropriate local treatment and 3 more courses of CMF or 4 courses of doxorubicin. Response was assessed by mammography. RESULTS: The overall response rate was 48% (a 3% pathologic complete response rate). Conservative surgery was achieved in 79.64% of the patients with a low rate of local disease recurrences (5%). Toxicity was minimal. With a median follow-up of 104 months, the 8-year disease-free survival (DFS) rate was 57.63% and the 8-year overall survival (OS) was 67.65%. The DFS and OS rates for patients with a clinical response were significantly longer, i.e., 70% (P=0.0048) and 90% (P=0.0042), respectively. CONCLUSIONS: PC with CMF was feasible. A high rate of breast-conservative surgery was achieved. The current results stressed the value of PC to increase conservative surgery and as a predictor of outcome.     

Liposomal paclitaxel versus docetaxel in induction chemotherapy using Taxanes,cisplatin and 5-fluorouracil for locally advanced nasopharyngeal carcinoma

Background

We wished to evaluate the efficacy and safety of liposomal paclitaxel and docetaxel for induction chemotherapy (IC) for nasopharyngeal carcinoma (NPC).

Methods

A total of 1498 patients with newly-diagnosed NPC between 2009 and 2017 treated with IC plus concurrent chemotherapy were included in our observational study. Overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and grade-3–4 toxicities were compared between groups using propensity score matching (PSM).

Results

In total, 767 patients were eligible for this study, with 104 (13.6%) and 663 (86.4%) receiving a liposomal paclitaxel-based and docetaxel-based taxanes, cisplatin and 5-fluorouracil (TPF) regimen, respectively. PSM identified 103 patients in the liposomal-paclitaxel group and 287 patients in the docetaxel group. There was no significant difference at 3?years for OS (92.2% vs. 93.9%, P?=?0.942), PFS (82.6% vs. 81.7%, P?=?0.394), LRFS (94.7% vs. 93.3%, P?=?0.981) or DMFS (84.6% vs. 87.4%, P?=?0.371) between the two groups after PSM. Significant interactions were not observed between the effect of chemotherapy regimen and sex, age, T stage, N stage, overall stage, or Epstein–Barr virus DNA level in the subgroup multivariate analysis. The prevalence of grade-3–4 leukopenia and neutropenia in the liposomal-paclitaxel group was significantly lower than that of the docetaxel group (P?<?0.05 for all).

Conclusions

Compared with docetaxel, liposomal paclitaxel has identical anti-tumor efficacy, but causes fewer and milder adverse reactions in IC for NPC.

     

A phase II study of ifosfamide, 5-fluorouracil and leucovorin in patients with recurrent nasopharyngeal carcinoma previously treated with platinum chemotherapy

The aim of this study was to evaluate the efficacy and toxicity of ifosfamide, 5-fluorouracil (5-FU) and leucovorin (IFL) as a second-line chemotherapy regimen in patients with recurrent undifferentiated nasopharyngeal carcinoma (NPC) previously treated with platinum/5-FU. Between June 1997 and February 1999, 18 patients were entered into the study. 3 patients had loco-regional recurrence, 12 had distant metastases and 3 had both loco-regional recurrence and distant metastases. All patients had previously received platinum/5-FU as adjuvant or palliative treatments. The IFL regimen consisting of ifosfamide 1.2 g/m(2) (with mesna), 5-FU 375 mg/m(2) and leucovorin 20 mg/m(2) for 5 days and was repeated every 21 days. The dose of ifosfamide was escalated to 1.4 and 1.6 g/m(2) in subsequent cycles according to the bone marrow toxicity, and the dose of 5-FU to 450 and 525 mg/m(2) according to the severity of mucositis. Patients received a median of 3 cycles of IFL (range: 2-6), with a median total ifosfamide dose of 21 g/m(2) (range: 13-46) and a median total 5-FU dose of 6.75 g/m(2) (range: 4.1-14.7). The median follow-up was 10 months (range: 4-25). 9 patients (50%) achieved a partial response and 1 patient (6%) achieved a complete response, with an overall response rate of 56% (95% confidence interval (CI): 32-80%). For those patients who responded to IFL, 8 had subsequent disease progression on follow-up, with a median response duration of 7.1 months (95% CI: 5.3-8.9). The median time to progression for all patients was 6.5 months (95% CI: 4.2-8.7). 12 patients are still alive with an estimated 1-year survival probability rate of 51%. Treatments were well tolerated, only 1 patient had grade 3 emesis. None of the patients had grade 3/4 anaemia, leucopenia or thrombocytopenia, although IFL was discontinued in 1 patient because of persisting thrombocytopenia. IFL is an effective second-line regimen in patients with recurrent NPC and is well tolerated with mild toxicity. Combining platinum and IFL in chemona?ve patients may further improve the overall response rate and duration and is worth investigating in future trials.     

A phase II trial of methotrexate, cisplatin, 5-fluorouracil, and leucovorin in the treatment of invasive and metastatic urothelial carcinoma

BACKGROUND: The current treatment of advanced urothelial carcinoma generates high response rates but is associated with poor overall survival. The current study evaluated the efficacy and toxicity of a new combination of active drugs in the treatment of urothelial carcinoma. METHODS: Twenty-four patients with muscle invasive or metastatic urothelial carcinoma were enrolled. Fifteen patients (63%) had metastatic disease whereas 9 patients had T2-T4 disease. Three patients were unevaluable for response because of significant toxicity. Patients were treated every 28 days with methotrexate, 60 mg/m(2), intravenously (i.v.) on Day 1; cisplatin, 25 mg/m(2)/day, by continuous i.v. infusion on Days 2-6; 5-flurouracil (5-FU) 800 mg/m(2)/day by continuous i.v. infusion on Days 3-6; and leucovorin, 500 mg/m(2)/day, by continuous i.v. infusion on Days 2-6. Dosage in subsequent cycles was adjusted according to toxicity. RESULTS: The median follow-up was 81 months (range, 53-97+ months). The overall response rate (complete response + partial response) for all 24 patients was 63% (95% confidence interval, 41-81%). The median survival was 65 months in the patients with muscle invasive disease and 17 months in the patients with metastatic disease. The duration of response in patients with metastatic disease was 6 months (range, 4-19 months). Toxicity was significant, with 82% of patients experiencing Common Toxicity Criteria Grade 3 or 4 neutropenia and 63% experiencing Grade 3 or 4 thrombocytopenia. However, only three patients developed febrile neutropenia and gastrointestinal and neurologic toxicity was moderate. CONCLUSIONS: The combination of methotrexate, cisplatin, 5-fluorouracil, and leucovorin represents an active regimen in the treatment of urothelial carcinoma with a moderate toxicity profile. As new drugs are found to treat urothelial carcinoma, further studies will be needed to evaluate the role of traditional agents such as 5-fluorouracil and methotrexate in new combination chemotherapeutic regimens.     

TPF方案诱导化疗加同期顺铂化放疗治疗晚期鼻咽癌的临床研究

 目的　探讨多西紫杉醇（TAX）、顺铂（DDP）、5-氟尿嘧啶（5-Fu）三药联合方案诱导化疗加DDP同期放化疗治疗晚期鼻咽癌的近期疗效及可行性。方法　40例初诊局部晚期（UICC分期Ⅲ、Ⅳ期）鼻咽癌患者入组,随机分为诱导化疗加DDP 3周方案组（A组）,诱导化疗加DDP单周方案组（B组）。两组均先行2个疗程诱导化疗,方案为TAX 60 mg／m2第1天;DDP 60 mg／m2第1天;5-Fu 600 mg／m2 第1天至第5天,每3周重复,共2个周期。第7周开始放疗,放疗第1天同时行化疗。A组：DDP 80 mg／m2第1天,每3周1次,共2次;B组： DDP 30 mg／m2第1天,每周1次,共6次。放疗采用二维适形照射,鼻咽原发病灶68～72 Gy,34～36次,7周,颈部淋巴结阳性区60～66 Gy,30～33次,6～6.5周。结果　40例共完成78个疗程诱导化疗,A、B组各1例出组。38例可评价疗效和不良反应。A组17例完成2个疗程同期DDP化疗;B组10例按计划完成6个周同期化疗,4例完成5周化疗,4例完成4周化疗,1例只完成2周化疗。诱导化疗后CR 4例（10.5 %）,PR 27例（71.1 %）,SD 7例（18.4 %）,总有效（CR+PR）率81.6 %。治疗结束后CR 32例（84.2 %）,PR 5例（13.2 %）,SD 1例（2.6 %）,总有效率 97.4 %。结论　TPF诱导化疗加DDP同期放化疗是治疗晚期鼻咽癌的可行方案,推荐使用同期DDP 3周化疗方案。剂量强度可否提高,有待进一步研究。     

鼻咽癌根治放疗后辅助化疗的疗效分析

目的 分析评价鼻咽癌根治放疗后辅助化疗的疗效。方法 A组(Ⅰ～Ⅱ期,38例)和B组(Ⅲ～Ⅳ期,122例)均首先接受根治放疗,其后A组治疗组(20例)和B组治疗组(64例)接受辅助化疗(LV+5-Fu+DDP)4个疗程。结果 A组中治疗组与对照组的3年和5年生存率分别为90％ vs88.9％和77.8％ vs 75％(P>0.05),B组中治疗组与对照组的3年和5年生存率分别为81.3％ vs63.8％和50.0％ vs 37.8％(P>0.05)。B组中,放射治疗后达到CR的治疗组与对照组的3年和5年生存率为82.4％ vs 76.7％和46.4％ vs 52.7％(P>0.05),非CR的治疗组与对照组的3年和5年生存率为80％ vs 50％和54.2％ vs 14.3％(P<0.05)。结论 对于根治性放疗后局部仍有残留的Ⅲ～Ⅳ期鼻咽癌患者,辅助化疗能提高生存率。     

Advanced colorectal carcinoma. A prospective randomized trial of sequential methotrexate, 5-fluorouracil, and leucovorin versus 5-fluorouracil alone

One hundred and twenty-five previously untreated patients bearing metastatic or advanced recurrent (inoperable) colorectal carcinoma and measurable disease were prospectively randomized. Those in arm A received 5-fluorouracil (5-FU), 1,200 mg/m2 i.v. infusion over 2 h, while those in arm B received methotrexate (MTX), 200 mg/m2 i.v. (push injection), followed 20 h later by 5-FU, 1,200 mg/m2 i.v. infusion over 2 h, plus calcium leucovorin (LV), 25 mg i.m. every 6 h for eight doses beginning 24 h after MTX administration. Cycles were repeated every 15 days. All patients receiving treatment were evaluable for toxicity and survival, and 118 patients were evaluable for response. The objective regression rate (complete plus partial response) was 12% (7 of 58) in arm A and 28% (17 of 60) in arm B (p = 0.049). No change was observed in 24% (14 of 58) in arm A and in 35% (21 of 60) in arm B (p = 0.28), while progressive disease was registered in 64% (37 of 58) and 37% (22 of 60) in arms A and B, respectively (p = 0.006). Median duration of response was 3 months in arm A and 5 months in arm B (p = 0.39). The median survival was 8.3 months in arm A and 11.2 months in arm B (p = 0.25). No statistically significant differences were found when objective regression and survival were related to site of primary tumor, performance status, and number of involved organs. There were two drug-related deaths in arm B due to severe myelosuppression followed by mucositis and sepsis. Of nonhematologic toxicities, diarrhea was more frequently observed in arm B, as were mucositis and infectious complications. Our results indicate that the sequential schedule MTX-5-FU-LV with 20-h intervals between MTX and 5-FU is superior in terms of objective regression to 5-FU alone given at the dose and schedule used in the present study. However, MTX-5-FU-LV did not have a significant impact on survival.     

Neoadjuvant chemotherapy with sequential methotrexate and 5-fluorouracil scheduling,epirubicin and cisplatin for locally advanced bladder cancer

INTRODUCTION: Transitional cell carcinoma of the bladder is moderately sensitive to chemotherapy. Notably, the methotrexate, doxorubicin, vinblastine and cisplatin regimen was found to produce a high overall response rate and a modest survival advantage. However, toxicity was significant and the therapy rarely results in long-term disease-free survival. In several clinical series, sequentially delivered methotrexate and 5-fluorouracil followed by leucovorin rescue in expectation of a biochemical modulation has a higher response rate. METHODS: The combination chemotherapy using sequential methotrexate and 5-fluorouracil scheduling, epirubicin and cisplatin (MFAP regimen) for locally advanced bladder cancer was evaluated in a neoadjuvant setting. Thirty-seven patients (32 males and 5 females) were enrolled in this study. RESULTS: Six (16.2%) of the patients had complete responses and 26 (70.3%) had partial responses to the therapy amounting to a response rate of 86.5%. At follow-up, 10 of 13 patients (76.9%) who underwent bladder preservation had not developed muscle-invasive recurrence of the disease and kept their bladder. There is no statistical difference of the survival rate between the cystectomy group and the bladder preservation group (p = 0.86). Toxicity was relatively mild but with some severe myelotoxic effects. CONCLUSIONS: MFAP represents an active regimen in the treatment of locally advanced bladder cancer with a moderate toxicity profile.     

CHEMOTHERAPY FOR ADVANCED NASOPHARYNGEAL CARCINOMA WITH METHOTREXATE, VINCRISTINE, CISPLATIN AND ADRIAMYCIN

Radiation therapy is the mainstay of treatment fornasopharyngeal carcinoma. With radiotherapy, the overall 5-year survival rate for stages I and II nasopharyngeal carcinoma is more than 80%. However, for the locally advanced (stages III and IV)cases, the 5-year survival rate is only 10%-40%. Death are due mainly to local-regional recurrence (about 47%) or distant metastasis （53%）[1-3]. Because the vast majority of nasopharyngeal carcinoma (>95%) is poorly differentiated squamous cell car…     

Concurrent cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy and radiotherapy for early breast carcinoma

PURPOSE: The optimal sequencing of adjuvant chemotherapy (CT) and radiation therapy (RT) in patients with early-stage breast cancer remains unclear. PATIENTS AND METHODS: We retrospectively compared 485 patients treated with conservative breast surgery and postoperative whole-breast RT and six courses of CMF (cyclophosphamide 600 mg/m(2), methotrexate 40 mg/m(2), and 5-fluorouracil 600 mg/m(2)) with 300 patients who received postoperative CMF only and with 509 patients treated with postoperative whole-breast RT only. The mean radiation dose delivered was 50 Gy (range, 46-52 Gy) with standard fractionation. The boost dose was 6-16 Gy according to resection margins and at the discretion of the radiation oncologist. Acute and late RT toxicity were scored using respectively the Radiation Therapy Oncology Group and the Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scale. RESULTS: A slightly higher Grade 2 acute skin toxicity was recorded in the concurrent group (21.2% vs. 11.2% of the RT only group, p < 0.0001). RT was interrupted more frequently in the CMF/RT group respective to the RT group (8.5% vs. 4.1%; p = 0.006). There was no difference in late toxicity between the two groups. All patients in the concurrent group successfully received the planned dose of RT and CT. Local recurrence rate was 7.6% in CT/RT group and 9.8% in RT group; this difference was not statistically significant at univariate analysis (log-rank test p = 0.98). However, at multivariate analysis adjusted also for pathological tumor, pathological nodes, and age, the CT/RT group showed a statistically lower rate of local recurrence (p = 0.04). CONCLUSIONS: Whole-breast RT and concurrent CMF are a safe adjuvant treatment in terms of toxicity.     

Sequential combination chemotherapy with methotrexate and 5-fluorouracil in advanced colorectal carcinoma

Twenty patients bearing advanced colorectal carcinoma, confirmed by histology, were evaluated after undergoing a sequential chemotherapeutic schedule which consisted of methotrexate, 200 mg/m2 in intravenous infusion during 4 h followed 1 h later by 5-fluorouracil, 600 mg/m2 in intravenous bolus. Twenty hours after ending the MTX administration, leucovorine, 14 mg/m2, was given intramuscularly every 6 h, in 8 doses. Courses were repeated every 15 days. Of 20 patients, 3 bearing colon carcinoma, without previous radiotherapy or chemotherapy, had a partial response. No change was registered in 6 cases. There was no significant difference in the survival of responders, those with stable illness and those with progression. Results were no better than those obtained with 5-fluorouracil used as a single drug and are in agreement with studies that established a 1-h interval between the administration of both drugs.     

5-fluorouracil modulated by leucovorin, methotrexate and mitomycin: highly effective, low-cost chemotherapy for advanced colorectal cancer

We have reported that an alternating regimen of bolus and continuous infusion 5-fluorouracil (FU) was superior to bolus FU in terms of response rate and progression-free survival in advanced colorectal cancer. Biochemical modulation was an essential part of this regimen and it was selective for the schedule of FU administration: bolus FU was in fact modulated by methotrexate (MTX) while continuous infusion FU was potentiated by 6-s-leucovorin (LV). Considering the low cost and the favourable report on the activity of mitomycin C (mito) added to CI FU, we have incorporated this agent in the infusional part of our treatment programme. 105 patients with untreated, advanced, measurable colorectal cancer were accrued from 13 Italian centres and treated with the following regimen. 2 biweekly cycles of FU bolus (600 mg/m(2)), modulated by MTX (24 h earlier, 200 mg/m(2)) were alternated with a 3-week continuous infusion of FU (200 mg/m(2)daily), modulated by LV (20 mg/m(2)weekly bolus). Mito, 7 mg/m(2), was given on the first day of the infusional period. After a 1 week rest, the whole cycle (8 weeks) was repeated, if indicated. 5 complete and 34 partial responses were obtained (response rate, 37% on the intention to treat basis; 95% confidence limits, 28-46%). After a median follow-up time of 26 months, 37 patients are still alive. The median progression-free survival is 7.7 months with an overall survival of 18.8 months and a 2-year survival rate of 30%. The regimen was very well tolerated with fewer than 13% of patients experiencing WHO grade III-IV toxicity. These results are consistent with those obtained by our group in 3 previous trials of schedule specific biochemical modulation of FU. They also indicate a highly active, little toxic, inexpensive regimen of old drugs to be used (a) as an alternative to the more expensive combinations including CPT-11 or oxaliplatin or (b) as the basis for combination programmes with these agents.     

Randomized controlled phase II comparison study of concurrent chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil versus CCRT with cisplatin, 5-fluorouracil, methotrexate and leucovorin in patients with locally advanced squamous cell carcinoma of the head and neck

We compared concurrent chemoradiotherapy (CCRT) with docetaxel, cisplatin (CDDP), and 5-fluorouracil (5-FU) (TPF) with CCRT with CDDP, 5-FU, methotrexate and leucovorin (PFML) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) in terms of safety and efficacy on survival. A total of 100 patients were enrolled. The TPF group received CCRT with the TPF regimen [docetaxel (50 mg/m²: day 1), CDDP (60 mg/m²: day 4), and continuous 5-FU infusion (600 mg/m²/day: days 1–5)]. In the PFML group, patients received CCRT with the PFML regimen [CDDP (60 mg/m²: day 4)], continuous 5-FU infusion (600 mg/m²/day: days 1–5), methotrexate (30 mg/m²: day 1) and leucovorin (20 mg/m²/day: days 1–5)]. Both groups received 2 cycles of chemotherapy during definitive radiotherapy. The total radiation dose was between 66.6 and 70.2 Gray. The overall response rates after CCRT were 98 with 90% of a pathologically complete response (pCR) in the TPF group and 94 with 77% in the PFML group. For grade 3/4 adverse events, mucositis was more frequent in the PMFL group, and the TPF group showed a higher incidence of hematological toxicity. CCRT with TPF or PMFL for advanced SCCHN was tolerable and produced excellent survival rates.     

Preradiation chemotherapy for pediatric patients with high-grade glioma

BACKGROUND: To evaluate the feasibility and efficacy of intensive chemotherapy given prior to irradiation in pediatric patients with malignant glioma, the Society of Pediatric Oncology in Germany started a randomized trial in 1991. The high-grade glioma strata had to be closed because of insufficient patient accrual. The follow-up data from these patients are reported. METHODS: Fifty-two patients with World Health Organization (WHO) Grade 4 malignant glioma (n = 27 patients) or with WHO Grade 3 anaplastic astrocytoma (n = 25 patients) between the ages of 3 years and 17 years were available for analysis. The tumor locations were supratentorial in 42 patients, the cerebellum in 8 patients, and the spinal cord in 2 patients (the brainstem was excluded). Tumor surgeries were biopsy in 10 patients, partial resection in 5 patients, subtotal resection in 10 patients, and macroscopic total resection in 21 patients. Patients received either 54 grays of irradiation (n = 22 patients) followed by chemotherapy with lomustine, vincristine, and cisplatin (maintenance chemotherapy) or sandwich chemotherapy (n = 30 patients), which consisted of ifosfamide, etoposide, methotrexate, cisplatin, and cytosine arabinoside followed by irradiation. RESULTS: The extent of resection was the most important prognostic factor. The median survival was 5.2 years for patients who underwent tumor resection of > or = 90% compared with 1.3 years for patients who underwent less than complete resection (P < 0.0005). After undergoing macroscopic total resection, sandwich chemotherapy (n = 15 patients) resulted in better overall survival (median, 5.2 years) compared with the maintenance protocol (n = 16 patients; median survival, 1.9 years; P = 0.015). A Cox multivariate regression analysis showed better survival for female patients (P = 0.025), WHO Grade 3 disease (P = 0.016), tumor resection of > or = 90% (P = 0.003), irradiation with > or = 54 grays (P = 0.003), and sandwich chemotherapy (P = 0.006). CONCLUSIONS: These data suggest that early, intensive chemotherapy increases survival rates in patients with malignant glioma who undergo complete resection.     

紫杉醇联合顺铂、5-氟尿嘧啶(TPF方案)新辅助化疗治疗晚期鼻咽癌的临床分析

目的:评价紫杉醇联合顺铂(DDP)、5-氟尿嘧啶(5-FU)(TPF方案)治疗晚期鼻咽癌的疗效和不良反应.方法:Ⅲ-Ⅳa 期鼻咽癌患者98例随机分为紫杉醇+顺铂+5-氟尿嘧啶新辅助化疗联合同期放化疗(治疗组)及以5-氟尿嘧啶+顺铂组成的同期放化疗组(对照组).新辅助化疗药用量:紫杉醇 135mg/m2,d1,顺铂20mg/m2,d1-5,5-氟尿嘧啶750mg/ m2,d1-5,每21天重复,治疗组所有病人均接受两个疗程TPF方案新辅助化疗.第2程新辅助化疗后14天即开始放疗.两组同期放疗相同.放疗采取 6MV X线常规照射,鼻咽部总剂量约 DT 70Gy/49天,颈部预防剂量约 DT 50-55Gy/35-42天,治疗剂量约 60-70 Gy/42-49天.比较两组疗效及不良反应.结果:治疗组鼻咽及颈部肿瘤消失的平均剂量小于对照组(P＜0.05) ;两组肿瘤临床全消率分别为87.8%与77.6%(P＜0.01).不良反应主要为粒细胞下降、脱发、口腔黏膜反应及胃肠道反应,均能耐受.结论:紫杉醇联合顺铂、5-氟尿嘧啶新辅助化疗治疗晚期鼻咽癌可提高肿瘤消失率,是治疗晚期鼻咽癌有效安全的方案.     

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

The combination of cisplatin and 5-fluorouracil (5-FU) (PF) is the most popular regimen for treating metastatic nasopharyngeal carcinoma (NPC) but it is limited by severe stomatitis and chronic cisplatin-related toxicity. A novel approach including induction with mitomycin C, doxorubicin and cisplatin (MAP) and subsequent maintenance with weekly 5-FU and leucovorin (FL) were designed with an aim to reduce acute and chronic toxicity of PF. Thirty-two patients of NPC with measurable metastatic lesions in the liver or lung were entered into this phase II trial. Mitomycin C 8 mg m(-2), doxorubicin 40 mg m(-2) and cisplatin 60 mg m(-2) were given on day 1 every 3 weeks as initial induction. After either four courses or remission was achieved, patients received weekly dose of 5-FU 450 mg m(-2) and leucovorin 30 mg m(-2) for maintenance until disease progression. With 105 courses of MAP given, 5% were accompanied by grade 3 and 0% were accompanied by grade 4 stomatitis. The dose-limiting toxicity of MAP was myelosuppression. Forty per cent of courses had grade 3 and 13% of courses had grade 4 leukopenia. No grade 3 or 4 cisplatin-related toxicity was observed. The overall response rate was 94% (95% confidence interval (CI) 84.9-100%) with a complete response rate (CR) of 6% (95% CI: 0-15.2%) and a good partial response (PR) rate of 28% (95% CI 11.7-44.6%), which was optionally defined as observance of only equivocal lesion identifiable under imaging study. Twenty-seven cases entered weekly FL maintenance phase. The median duration of maintenance with weekly FL was 38 weeks (8-91 weeks). There was no grade 3 or 4 toxicity noted during weekly FL. The median progression-free survival and overall survival were 11.6+/-0.4 and 18.1+/-3.6 months respectively. Six patients with a median follow-up of 19.8 months (9.6-41.0 months) were still alive and five of them had disease under control with FL. Good responders (CR and good PR) had better survival than less satisfactory responders (PR and stable disease) (P = 0.05). From Cox's multivariate regression analysis, the only significant prognostic factor for survival was good response to MAP (P = 0.042). Liver metastasis was the only significant variable in the best subset regression model that predicted good response to MAP (CR and good PR) (P = 0.027). MAP was an effective combination for metastatic NPC with minimal stomatitis and cisplatin-related toxicity but had significant myelosuppression. Weekly FL was a maintenance therapy with minimal side-effects. The response rate and overall survival of MAP-FL were better than series previously reported even when a subset of patients with poor prognosis was selected. MAP-FL's role as neoadjuvant or adjuvant therapy is worthy of further study.