Cisplatin, doxorubicin, and 5-fluorouracil chemotherapy for salivary gland malignancies: a pilot study of the Northern California Oncology Group

Seventeen patients with advanced or recurrent salivary gland cancer were treated with cisplatin, doxorubicin, and 5-fluorouracil combination chemotherapy (PAF). Two patients achieved a complete response and four patients achieved a partial response, for an overall response rate of 35%. Six of the nine patients who received PAF in the neoadjuvant setting did not respond and proceeded to surgery and/or radiation therapy. No difference in response rate was found between those patients treated for recurrent disease v those treated with neoadjuvant chemotherapy. All three patients with adenocarcinoma responded. The response duration in patients with metastatic or recurrent disease ranged from 6 to 15 months. The PAF regimen was delivered primarily in the outpatient setting and was associated with acceptable toxicity. PAF demonstrates activity in salivary gland malignancies, and further evaluation of this combination seems warranted.     

Fluorouracil, doxorubicin, cyclophosphamide, and cisplatin combination chemotherapy in advanced or recurrent salivary gland carcinoma

Seventeen patients with recurrent or unresectable salivary gland carcinomas were treated with combination fluorouracil (5-FU), doxorubicin, cyclophosphamide, and cisplatin (FACP). Sixteen patients were assessable for response and toxicity. A total of 111 courses of chemotherapy were given, yielding one complete and seven partial responses, for an objective response rate of 50%. Two other patients had stable disease and two had a minor response. The median duration of objective response was 32 weeks (range, 4 to 72); median survival for the 16 patients was 72 weeks. Hematologic toxicity was significant, with 88% developing a nadir granulocyte count of less than 1,000 cells per microliter (median, 300 cells per microliter), and 53% a nadir platelet count of less than 100,000 cells per microliter (median, 68,000 cells per microliter). Seven patients (44%) developed neutropenic fever, and three (18%) developed an increase in serum creatinine greater than 1.5 mg/dL during the course of treatment. This combination of chemotherapy was active; however, an increased response rate was not observed above that reported for other combinations. Response duration, or overall patient survival, on this intensive regimen was similar as compared with other published therapeutic trials of this disease entity.     

Cisplatin and 5-fluorouracil chemotherapy in advanced or recurrent squamous cell carcinoma of the head and neck

Fifty-three patients with advanced or recurrent squamous cell carcinoma of the head and neck (SCCHN) were treated with bolus cisplatin (CDDP) and 96-hour infusion of 5-fluorouracil (5-FU). Twenty-six patients with advanced disease (21 T4 and/or N3) and no prior therapy (NPT) received 2 to 3 cycles of chemotherapy prior to surgery and/or radiation. There were four complete responses (CR) and 12 partial responses (PR) to chemotherapy for an overall response rate of 61%. In 20 patients with locally recurrent or disseminated disease there was one CR and six PR for an overall response rate of 35%. All but one responding patient in both groups showed clear evidence of tumor response after the initial cycle of chemotherapy. Two of the five complete responders required at least three courses to achieve CR. Disease-free survival was poor: only five of 26 patients in the NPT group remain alive and free of disease 8 to 28 months from initial therapy. CDDP and 5-FU is an active combination for SCCHN, but survival benefit remains to be proven.     

Paclitaxel, 5-fluorouracil, and cisplatin combination chemotherapy for the treatment of advanced gastric carcinoma

BACKGROUND: Although the clinical efficacy of paclitaxel in the treatment of gastric carcinoma has not been clearly defined, recent reports have suggested a possible role in the treatment of upper gastrointestinal carcinomas in vitro and in vivo. In this study, the authors evaluated the efficacy and toxicity of a combination chemotherapy that included paclitaxel, 5-fluorouracil (5-FU), and cisplatin in the treatment of patients with advanced gastric carcinoma. METHODS: Forty-one gastric carcinoma patients with metastatic disease, unresectable advanced disease, or relapsed disease were treated with the following regimen, administered every 28 days: paclitaxel 175 mg/m2 by 3-hour intravenous (i.v.) infusion on Day 1, 5-FU 750 mg/m2 by 24-hour continuous i.v. infusion on Days 1-5, and cisplatin 20 mg/m2 by 2-hour i.v. infusion on Days 1-5. Twenty-six patients had measurable disease, and 15 had evaluable disease. All patients were assessable for toxicity. RESULTS: Twenty-one of the 41 patients (51%; 95% confidence interval [CI], 36.5-65.7%) demonstrated an objective response, including 4 complete responses (10%; 95% CI, 3.9-22.5%). Sixty-five percent of the patients with measurable disease (17 of 26; 95% CI, 58-92.5%) and 27% of the patients with evaluable disease (4 of 15: 95% CI, 11.1-52.3%) achieved a complete response or a partial response. The median response duration was 17 weeks (range, 4-90 weeks), and the median survival duration for all patients was 26 weeks (range, 8 to 118+ weeks). The major toxicity of this treatment was myelosuppression with neutropenia of World Health Organization Grade 3 and 4 in 24% and 10% of the patients, respectively. Nonhematologic toxicity included mucositis, nausea/vomiting, diarrhea, neurotoxicity, and alopecia. Fluid retention occurred in two patients, and one patient had an anaphylatic reaction. Dose reduction was necessary for one patient, because Grade 4 neutropenia and mucositis occurred. CONCLUSIONS: Paclitaxel, 5-FU, and cisplatin was an active combination regimen in the treatment of advanced gastric carcinoma. The toxicity of this regimen was tolerable. Based on these findings, this combination regimen could be an attractive treatment in the preoperative setting.     

Biweekly low-dose cisplatin and 5-fluorouracil combination chemotherapy for advanced gastrointestinal carcinoma

Biweekly intravenous infusions of low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) were evaluated in 80 patients with advanced or recurrent gastric, colorectal, pancreatic or gallbladder adenocarcinoma. CDDP was given biweekly at a dose of 15 mg/m2 infused for 30 minutes, and 5-FU 375 mg/m2 was infused for 2 hours as many times as possible. The response rate among patients with gastric cancer was 26%, colorectal cancer 10%, pancreatic cancer 7.7%, and gallbladder cancer 42.9%. The response rates were not so high, but the median survival time of patients with recurrent gastric cancer was 17.3 months, pancreatic cancer 6.7 months, and gallbladder cancer 10.7 months. A patient with unresected advanced pancreatic head cancer with liver and para-aortic lymph node metastases received this therapy 38 times, and lived for 54 months. No severe side effects occurred in any of these cases. Thus, this chemotherapy could well be effective for the outcome of cases of advanced gastrointestinal carcinoma.     

Results of initial doxorubicin, 5-fluorouracil, and cyclophosphamide combination chemotherapy for inflammatory carcinoma of the breast

Forty-three patients with nonmetastatic inflammatory breast carcinoma have been treated by initial doxorubicin, 5-fluorouracil, and cyclophosphamide (FAC) combination chemotherapy. After three chemotherapy cycles, responding patients underwent surgery. Chemotherapy was then completed for nine cycles of FAC followed by locoregional radiation therapy. All patients received tamoxifen 40 mg/day for 1 year from the time of diagnosis. Thirty-eight patients (88%) had a clinical response to chemotherapy and underwent surgery. On histologic examination 17 patients had a residual tumor mass less than 1 cm diameter or a complete tumor disappearance; lymph nodes dissection was negative in 15 patients. With a median follow-up of 48 months, the predicted 5-year disease-free survival (DFS) is 48% (median DFS, 46 months). Analysis of prognosis factors shows that age, menopausal status, and histologic grade have no predictive value. The DFS and overall survival were significantly improved by the presence of hormonal receptors and a low number of positive lymph nodes (less than 4) at surgery. The most significant prognosis factor was the residual tumor mass after initial chemotherapy with an 80% predicted 5-year DFS for the responding patients versus 30% for the no responding patients (P less than 0.001).     

Cisplatin and 5-fluorouracil in advanced and recurrent cervical cancer

Nineteen consecutive patients with advanced or recurrent cervical cancer were treated with cisplatin 20 mg/m2 plus 5-fluorouracil 200 mg/m2 on days 1-5 every 3 weeks. Toxicity was acceptable and manageable, with most patients treated on an outpatient basis. The most important side effect was dose-cumulative neurotoxicity. In 18 evaluable patients a 61% objective response rate (1 complete and 10 partial) was achieved. In recurrent disease the regimen was effective both in irradiated lesions and in non-irradiated ones. Two out of five patients not previously treated with radiotherapy and/or chemotherapy responded to the treatment but tumor regression was insufficient for the disease to be controlled radically by subsequent surgery or radiotherapy. The median duration of response was 11 months (3-23) and the actuarial survival rate after 36 months follow-up was 43.3%.     

Cisplatin, epirubicin, leucovorin and 5-fluorouracil (PELF) is more active than 5-fluorouracil, doxorubicin and methotrexate (FAMTX) in advanced gastric carcinoma.

BACKGROUND: 5-Fluorouracil (5-FU), doxorubicin and methotrexate (FAMTX) and cisplatin, epirubicin, leucovorin and 5-FU (PELF) have both been reported to be superior to the combination 5-FU, doxorubicin and mitomycin C (FAM) in advanced gastric carcinoma. On the basis of the presence and dose intensity of the included agents, we hypothesised that PELF would be superior to FAMTX. PATIENTS AND METHODS: Two hundred patients with untreated advanced gastric carcinoma were randomised to receive PELF or FAMTX for a maximum of six cycles or until disease progression. RESULTS: The complete response (CR) rates to PELF and FAMTX were, respectively, 13% [95% confidence intervals (CI) 6% to 20%] and 2% (95% CI 0% to 5%; P = 0.003), and the objective response rates [CR plus partial response (PR) rates] 39% (95% CI 29% to 49%) and 22% (95% CI 13% to 30%; P = 0.009), thus significantly favouring the PELF combination. The survival rates after 12 months (30.8% versus 22.4%) and 24 months (15.7% versus 9.5%) were also higher among patients receiving PELF, but these differences were not statistically significant. The toxicities were qualitatively different but quantitatively similar. Both regimens seem to be feasible provided that careful patient monitoring is assured. CONCLUSIONS: PELF is significantly more active than FAMTX and deserves further research in the adjuvant setting.     

Effect of combination of 5-fluorouracil, epirubicin and mitomycin C (FEM) on advanced gastric carcinoma

Fifteen patients with advanced gastric carcinoma were treated with the combination of 5-Fluorouracil (5-FU), Epirubicin (EPI) and Mitomycin C (MMC). Twelve of 15 patients were evaluable. Three patients showed partial response (25%) and 4 showed no change (33%) according to the criteria of Japan Society for Cancer Therapy. Mean survival time for responders, nonresponders and all evaluable patients were 14. 3, 3.6 and 6.3 months, respectively. Two patients with partial response lived over 18 months. Major toxicities included myelosuppression, nausea and vomiting, and alopecia. These were mild in general and reversible by discontinuance. No cardiotoxicity developed. It was concluded that this combination therapy is beneficial in patients with advanced gastric carcinoma because it showed measurable clinical effectiveness with less toxicity than FAM therapy (a combination of 5-FU, Doxorubicin and MMC).     

Prospective evaluation of chronic cardiotoxicity due to high-dose epirubicin or combination chemotherapy with cyclophosphamide,methotrexate, and 5-fluorouracil

Summary In a prospective study the left ventricular ejection fraction (LVEF), right ventricular ejection fraction (RVEF), systolic blood pressure, ECG, and heart rate were recorded at rest and during submaximal work to compare the cardiotoxic effect of epirubicin with a combination chemotherapy without known cardiotoxicity. A total of 14 females with advanced breast cancer were treated with epirubicin at a median cumulative dose of 827 mg/m² (range, 550–1244). These patients had previously received cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) or cyclophosphamide alone as adjuvant treatment, or CMF for advanced disease. The control group consisted of 11 females with advanced breast cancer given CMF only. The systolic blood pressure at rest as well as during submaximal work was significantly lower (P(0.05) after treatment in the epirubicin group than in the CMF controls. With regard to LVEF, the median value of 54% at rest was significantly lower after treatment in the epirubicin group than in the controls (59%). There was a significant fall in LVEF at rest and during exercise in the epirubicin group, whereas no such changes were found in the CMF controls after treatment. The RVEF was unaffected. In the epirubicintreated group one patient developed fatal congestive heart failure, and in the remaining 13 patients treatment was discontinued due to progression of the cancer and not to cardiotoxicity. Thus, the cardiotoxicity of epirubicin changed the clinical outcome in only 1 of 14 patients with advanced breast cancer.     

Multicenter phase II trial of combination chemotherapy with weekly paclitaxel and 5-fluorouracil for the treatment of advanced or recurrent gastric carcinoma

The aim of this study was to investigate the efficacy and safety of combination chemotherapy with weekly paclitaxel and 5-fluorouracil (5-FU) as first-line treatment in patients with advanced or recurrent gastric carcinoma. A total of 65 patients were treated with the following regimen, administered every 28 days; 5-FU 600 mg/m2 by 24-hour continuous infusion from days 1 through 5, and weekly paclitaxel 80 mg/m2 by 3-hour intravenous infusion on days 8, 14, and 21. A total of 272 cycles were conducted with a median of 4 (2-13) cycles per case. Out of 57 patients with measurable disease by RECIST criteria, there were 2 complete responses (3.5%), 20 partial responses (35.1%) and 25 cases with stable disease (43.9%). The overall response rate was 38.6% (95%CI: 26.0-51.2%). The median survival time and 1-year survival rates were 329 days and 47.4%, respectively. Both hematologic and non-hematologic toxicities were well tolerated.     

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.     

Treatment of metastatic breast cancer with the combination of ifosfamide, epirubicin and 5-fluorouracil

An ongoing trial of combination chemotherapy using ifosfamide (Holoxan), epirubicin and 5-fluorouracil was started in 1987. A total of 30 patients with metastatic cancer of the breast received 1.5 g/m² i. v. ifosfamide over 60 min on days 1–3, 50 mg/m² i. v. epirubicin on day 1 and 500 mg/m² i. v. 5-fluorouracil on day 1, followed by mesna (Uromitexan) given at 20% of the ifosfamide dose at 0, 4 and 8 h. The courses were repeated every 4 weeks. In all, 198 courses were given, ranging from 3 to 13 (median, 7) cycles/patient. The mean age of the 30 patients was 48 years (range, 35–66 years); 5 had not previously received chemotherapy and the others had failed prior cytotoxic and endocrine therapy. Overall, 28 patients were evaluable, 7 (25%) showed a complete response and 15 (54%) had a partial response, for an overall response rate of 22/28 (79%). Three patients showed stable disease with improved symptoms, and in three cases disease progression occurred. The median duration of response was 9 months (range, 3–20 months). Median survival was 11 months for all patients, 15 months for CRs, 10 months for PRs, 6 months for stable disease and 12 months for progressive disease (PD). Survival for the 22 responding patients was 12 months. Toxicity was acceptable and included alopecia, mucositis, nausea, vomiting, diarrhoea, mild cystitis and myelosuppression. Epirubicin did not appear to produce cardiac toxicity, and ifosfamide with mesna did not seem to result in severe urotoxicity. Chemotherapy with ifosfamide, epirubicin and 5-fluorouracil proved to be effective for treatment of advanced breast cancer and should be further studied in large, controlled trials.Presented at the Satellite Symposium Ifosfamide in Gynecological Tumors of the 5th European Conference on Clinical Oncology and Cancer Nursing, London, September 3–7, 1989     

Phase II trial of chemotherapy with 5-fluorouracil, bleomycin, epirubicin, and cisplatin for patients with locally advanced, metastatic, or recurrent undifferentiated carcinoma of the nasopharyngeal type.

BACKGROUND: The aim of this study was to evaluate the toxicity and efficacy of the combination of 5-fluorouracil, bleomycin, epirubicin, and cisplatin (FBEC) in the treatment of patients with undifferentiated carcinoma of nasopharyngeal type (UCNT). The study included patients with metastatic or recurrent disease (Group A) and previously untreated patients with locally advanced nonmetastatic disease (T >/= 3 or any T, N >/= 2, M0, according to 1987 criteria of the International Union Against Cancer and the American Joint Committee on Cancer (Group B). METHODS: From January 1992 to November 1996, 49 patients with histologically proven UCNT were treated with intravenous (i.v.) 5-fluorouracil (700 mg/m(2)/day by continuous infusion for 4 days), epirubicin (70 mg/m(2) i.v. on Day 1), Bleomycin (10 mg i.v. bolus on Day 1 followed by 12 mg/m(2)/day by continuous infusion for 4 days), and cisplatin (100 mg/m(2) on Day 5); this regimen was repeated every 21 days. Six cycles were given to Group A (26 patients), with bleomycin omitted during the last 3 cycles. In Group B (23 patients), only 3 cycles were given, followed by conventional radiotherapy (70 gray for 7 weeks). RESULTS: Of the 26 patients entered in Group A, 23 were evaluable for response. Nine complete responses (CRs) and 9 partial responses (PRs) were assessed, for a 78% objective response rate (ORR) (95% CI: 56-92). Three patients are alive with no evidence of disease after 43, 61, and 73 months, respectively. These patients achieved a CR with chemotherapy followed by consolidating radiotherapy to their target lesions. In Group B, the ORR was 91.5%, with 5 CRs (22%) and 16 PRs (69.5%) assessed in the 23 patients. Three months after the end of radiotherapy, the ORR was 87% (20 patients). After a median follow-up of 51 months (range, 24-67 months), 15 patients (65%) are alive without evidence of disease. Forty percent of cycles (51% in Group A, 25% in Group B) resulted in Grade 4 neutropenia, with fever and/or sepsis in 9.5%. Mucositis was seen in 42% of pretreated patients. There were 3 treatment-related deaths (2 from complications of infection and 1 bleomycin fibrosis at a total dose of 160 mg/m(2)), all of them in Group A. CONCLUSIONS: The FBEC regimen has good activity, with durable responses in patients with locally advanced, metastatic, or recurrent UCNT. This regimen is safe for patients with locally advanced disease, but close follow-up and supportive measures are needed when it is used to treat those with metastatic or recurrent disease.     

Cisplatin, mitomycin-C, 5-fluorouracil and leucovorin combination chemotherapy (l-FCM) in locally advanced unresectable or metastatic gastric carcinoma: a phase-II study

Despite relevant progress, the impact of chemotherapy on advanced gastric cancer patients' survival is still unsatisfactory. Thus, the key objective of our efforts should be palliation of the symptoms and the maintenance of an adequate quality of life. In this phase-II study, we evaluated toxicity and efficacy of the combination of cisplatin, fluorofolates and mitomycin C. Thirty-one advanced gastric cancer patients received cisplatin (15 mg/m2) and 5-fluorouracil (350 mg/m2), both for 5 consecutive days every 4 weeks; 5-fluorouracil infusion was preceded by a rapid i.v. injection of 100 mg/m2 leucovorin, while mitomycin-C (10 mg/m2) was administered on day 1 of odd cycles. Cycles were repeated every 4 weeks until disease progression. We recorded 16 objective responses (51.6%, 95% confidence interval: 42.63-60.57); furthermore, such a response rate was coupled with a moderate degree of toxicity and an extremely good tolerance. In particular, alopecia, a frequent and distressing side-effect in patients, especially women, in our series occurred only in two patients. This treatment appears to be an active and tolerable therapeutic option for patients with advanced gastric carcinoma.     

Cisplatin, epirubicin, and lonidamine combination regimen as first-line chemotherapy for metastatic breast cancer: a pilot study

 We assessed the activity and tolerability of a cisplatin, epirubicin, and lonidamine combination regimen as first-line chemotherapy in 28 advanced breast cancer patients. The schedule of treatment was as follows: 60 mg/m² epirubicin followed by 40 mg/m² cisplatin given on days 1 and 2 every 21 days, with 450 mg lonidamine being given per os (three tablets) on days of chemotherapy administration and in the period intervening between one cycle and the next. Patients received a median of 5 (range 1 – 6) cycles. Overall, 22 patients were evaluable for response and 28, for toxicity. Four patients refused to continue the treatment after the first course, one was lost to follow-up, and one died due to toxicity (septic shock). The incidence of grade 3/4 nausea and vomiting was found to be greater than that expected with epirubicin and lonidamine alone. The addition of cisplatin resulted in an increase in platelet and hemoglobin toxicities, whereas the WBC toxicity did not differ from that expected with epirubicin and lonidamine. The hematological toxicity was found to be cumulative, leading to treatment delay in about 50% of patients at the fifth and sixth courses. The activity of this cytotoxic regimen was noteworthy, with the overall response rate being 81.8% (31.8% complete responses and 50.0% partial responses) in evaluable patients. This response rate decreased to 64.2% when all registered patients were included according to an intent-to-treat analysis. In conclusion, the association of cisplatin, epirubicin, and lonidamine given on the schedule described herein, appears to be very active but substantially toxic. We are now testing this combination in a randomized comparison, with the cisplatin dose being reduced to 30 mg/m² given on days 1 and 2. Received: 1 January 1997 / Accepted: 22 July 1997     

Cyclophosphamide, doxorubicin, and cisplatin combination chemotherapy for advanced carcinomas of salivary gland origin

Thirteen patients with carcinomas of major and minor salivary gland origin (nine adenoid cystic carcinomas and four adenocarcinomas) were treated with cyclophosphamide (500 mg/m2), doxorubicin (50 mg/m2), and cisplatin (50 mg/m2) (CAP) by intravenous injections on the first day of a 28-day regimen. Sixty-one cycles of CAP were administered (mean, 4.7 cycles per patient). Eleven patients were treated for palliation of recurrent disease (locoregional, ten; lung, ten; liver, three; and bone, three). Two patients untreated previously, one with extensive local disease involving the base of the skull and one with a solitary lung metastasis (resected with a positive margin) and an initially unappreciated base of tongue primary, received two cycles of CAP followed by local treatment and adjuvant CAP. Previous therapy for the 11 patients with recurrent disease included surgery (ten), radiotherapy [RT(11)], chemotherapy (three), or hormonal therapy (two). Three complete and three partial responses to chemotherapy were noted for an overall response rate of 46%. The median duration of response in palliative patients was 5 months (range, 2 to 9). Of the two patients receiving induction CAP, one relapsed with distant disease 26 months after treatment, and the other remains disease-free after 60 months of follow-up examination. Chemotherapy was well tolerated generally, and no chemotherapy-related deaths occurred. One hypertensive patient suffered a stroke after 3 cycles of therapy. CAP is an active regimen against salivary gland carcinomas and deserves further study. Also, it may be of value as induction or adjuvant treatment for patients with advanced disease untreated previously.     

Cisplatin, vindesine, and 96-h continuous infusion of 5-fluorouracil as initial chemotherapy for locally advanced head and neck carcinoma

The combination of cisplatin (80 mg/m2, i.v., day 1), 96-h infusion of 5-fluorouracil (5-FU) (30 mg/kg/24 h) and vindesine (3 mg/m2 days 1 and 8) was evaluated in 31 patients with histologically proven epidermoid carcinoma of the head and neck. All patients were nonpretreated and had measurable lesions. Three (10%) of the 29 evaluable patients achieved a complete response (CR) and 19 (66%) had partial response (PR) with an overall response rate (CR + PR) of 76%. The major toxicity was leukopenia. Median overall survival was 14.5 months. It is concluded that the combination of cisplatin, 96-h infusion of 5-FU, and vindesine was as effective as other regimens including 5-FU and cisplatin reported in the literature, with a similar toxicity. The low CR rate in this trial is related to the high percentage of T4 N3 disease.     

Phase II trial combining mitomycin with 5-fluorouracil, epirubicin, and cisplatin in recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type

Background: This phase-II study was conducted to investigate the potential benefit from the addition of mitomycin to a conventional anthracycline-cisplatin- and 5-fluorouracil-based chemotherapy for recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type (UCNT).Patients and methods: Between July 1989 and December 1991, 44 consecutive patients (M/F 36/8; median age: 45, range 20–72; performance status (PS) 0: 20 patients, PS 1: 14 patients, PS 2: 10 patients) with recurrent or metastatic UCNT were entered in this study after complete clinical, biological, and radiological pre-therapeutic work-ups. Chemotherapy (FMEP regimen) consisted of 800 mg/m2/day 5-fluorouracil in continuous infusion from day 1 to day 4 combined with 70 mg/m2 epirubicin, 10 mg/m2 mitomycin, and 100 mg/m2 cisplatin on day 1, every four weeks for six cycles. Mitomycin was delivered in cycles 1, 3, and 5 only. Eleven patients had isolated loco-regional recurrences, 12 patients had local recurrences associated with distant metastasis, and 21 patients had metastasis only. Toxicity and response were evaluated according to WHO criteria.Toxicity: Grade 3–4 neutropenia was observed in 122 of 212 evaluable cycles (57%) and 39 of 44 patients (89%); febrile neutropenia occurred in 16 patients (36%) and 24 cycles (11.3%). Grade 3–4 thrombocytopenia was observed in 27 patients (61%) and 45 cycles (21%), including 27 of 45 cycles (60%) with mitomycin. Grade 3 anemia was noted in 18 patients (40%) and 23 cycles (11%), including 18 of 23 cycles (78%) with mitomycin. Grade 3–4 mucositis occurred in 25 cycles (11%) and 14 patients (32%), mainly in those previously treated with radiation therapy in the head and neck area. There were four treatment-related deaths (9%); three of them neutropenia-related, and one of cardiac toxicity.Response: Forty-four patients were evaluable for response: There were 23 of 44 objective responses (52%), including six complete responses (13%), and 17 partial responses (38%). Additional radiotherapy was given to 13 patients after documentation of response: Nasopharyngeal tumor + cervical nodes (eight patients) and/or on bone metastasis sites (five patients); mediastinal lymph nodes (one patient). At a median follow-up of 87 months (range 71–100), five patients are alive and in continuous complete remission. The median survival time was 14 months and the median time to progression nine months.Conclusion: The regimen under study is active in recurrent/metastatic UCNT, but associated with excessive toxicity.