Analysis of efficacy and toxicity of chemotherapy with cisplatin, 5-fluorouracil, methotrexate and leucovorin (PFML) and radiotherapy in the treatment of locally advanced squamous cell carcinoma of the head and neck

Purpose The aim of this study was to evaluate the efficacy and toxicity of concurrent chemoradiotherapy using cisplatin (CDDP), 5-fluorouracil (5-FU), methotrexate (MTX) and leucovorin (LV) (PFML) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Methods Seventy-seven patients with previously untreated stages III–IV SCCHN were included in this trial. Patients received two cycles of chemotherapy repeated every 4 weeks. The chemotherapy regimen consisted CDDP (60 mg/m², day 4), 5-FU (600 mg/m² given over 24 h for 5 days, days 1–5), MTX (30 mg/m², day 1) and LV (20 mg/m², days 1–5). Radiation was targeted to begin on the starting day of chemotherapy, day 1. The total radiation dose to the primary site and neck lymph nodes was 70.0 Gy. When grade ≥3 toxicities were observed frequently, radiotherapy and/or chemotherapy were delayed or reduced. Results The main toxicities were mucositis (grade ≥3, 39%), leukocytopenia (grade ≥3, 34%) and neutropenia (grade ≥3, 30%). The overall clinical response rate and the pathological complete response (CR) were 94% (72/77) and 71% (55/77). The primary site CR and neck lymph node CR were 79% (61/77) and 85% (44/52), and 3-year survival rate was 73%. Conclusions This concurrent chemoradiotherapy with PFML was safe and well tolerated. The high CR rate justifies further evaluation of this chemoradiotherapy modality in locally advanced SCCHN patients.     

Sequential Methotrexate and 5-Fluorouracil as Second-Line Chemotherapy for Advanced Colorectal Cancer Patients Pretreated with 5-Fluorouracil and Leucovorin: a GISCAD Study

Abstract

The biochemical modulation of 5-fluorouracil (5-FU) by means of methotrexate (MTX) and 6-S leucovorin (LV) seems mainly directed at two different intracellular targets, supporting the hypothesis of possible non-cross resistance between these two methods of 5-FU potentia-tion. Thirty-one patients, all previously treated with 5-FU and LV for advanced colorectal cancer (ACC), were treated with MTX=200 mg/m² iv day 1 and 5-FU 600 mg/m² day 2 with 6-S LV 10 mg/m² po q 6 h X 6 starting 24 h after MTX, repeated every 2 weeks. Of 30 eva-luable patients, 2 Partial Remissions (PR) were achieved (Response Rate=6.6%; 95% Confidence Interval 0%-14%). Eight patients had disease stabilization (SD). The overall median survival was 5 months (range 1-11). No WHO grade III-IV toxicities were reported. Despite the good tolerability, this combination of MTX, 5-FU and LV rescue has minimal activity in ACC after the failure of 5FU+LV-based chemotherapy.     

A case of rectal cancer with multiple liver and peritoneal metastases that responded dramatically to low-dose 5-FU plus LV and CDDP combination chemotherapy

We have experienced successful treatment of a multiple hepatic metastasis of rectal cancer with combination chemotherapy. The patient is a 57-year-old male with bowel obstruction accompanied by rectal cancer (SE, N3, P1, H3, M (-) stage IV) who underwent a Hartmann operation with D3 lymph node dissection on July 6, 2000. The histopathological findings revealed a well-differentiated adenocarcinoma (se, INFbeta, n3, ly2, v2, p1). From the 11th postoperative day, combination chemotherapy using 5-FU 750 mg/day and LV 300 mg/day was performed once a week. When he underwent 5 combination chemotherapy treatments, adverse effects of grade 3 occurred, and the serum CEA level rose rapidly. We changed his regimen at that time. He underwent 2 courses of combination chemotherapy with 5-FU 500 mg/day and CDDP 10 mg/day for 5 days. Additional courses of combination chemotherapy with 5-FU 500 mg/day, LV 25 mg/day and CDDP 10 mg/day were performed weekly in the outpatient department. The treatment was effective, and a complete response (CR) was noted 4 months after the chemotherapy. The same combination chemotherapy was performed biweekly for one year after CR. The patient has been receiving a subsequent single administration of UFT and has remained in remission for 3 years and 7 months after surgery.     

Combination chemotherapy with 5-FU and low-dose CDDP for urogenital tumors]

Chemotherapy with 5-FU and low-dose CDDP, MTX or LV has not been fully evaluated in urogenital tumors. In a study of advanced renal cell carcinoma, the response rate of the combination of 5-FU, CDDP and IFN-alpha was 9%. In urinary bladder cancer, the combination chemotherapy with 5-FU and low-dose CDDP has been used as a radiosensitizer. This combination chemotherapy with radiation introduced a high response rate and has been used for the preservation of bladder function with minimum invasive surgery. There are very few effective chemotherapies for advanced androgen independent prostate cancer. However, some oral fluoripyrimidine, like UFT, was shown to be effective to some extent for prostate cancer in a phase II study. Thus, combination therapies of 5-FU and low-dose CDDP for prostate cancer as a biochemical modulator may be expected.     

Low-dose CDDP and 5-FU for head and neck cancer patients]

Combination chemotherapy with CDDP and 5-FU is one of the most effective regimens for head and neck cancer. Recent studies have focused on biochemical modulation in the combination of CDDP and 5-FU. We studied the difference in effectiveness and adverse effects between two CDDP administration schedules for CDDP-5-FU combination chemotherapy. For regimen A, CDDP was administered on 5 consecutive days from day 1 to day 5, with a daily dose of 16 mg/m2. For regimen B, CDDP was administered at 80 mg/m2 on day 1. 5-FU was administered at 600 mg/m2/day in a continuous drip infusion for 120 hours from day 1 to day 5 for regimens A and B. Twenty-seven patients with head and neck squamous cell carcinoma were included in this study, and received either regimen A or B. Thirteen patients were given regimen A and 14 regimen B. With regimen A, 3 patients showed CR and the response rate was 76.9%. With regimen B, 3 patients showed CR and the response rate was 64.3%. The rates of efficacy were not different between regimen A and B. In contrast, a difference was seen with organ toxicity. Regimen B was more toxic for renal function than regimen A, while regimen A showed greater toxicity to bone marrow function. Acute nausea and vomiting were observed more frequently with regimen B. The difference in organs and symptoms of adverse effects, according to the schedule of CDDP administration would seem to be important in the treatment of head and neck cancer patients. The schedule of CDDP administration should be adjusted depending on the renal and bone marrow functions of the patients. Because multiple infusion of CDDP proved to be efficacious, low-dose CDDP and 5-FU will have a role for patients with head and neck squamous cell carcinoma. We also introduce other reports on the efficacy of low-dose CDDP and 5-FU.     

Results of a Five-Drug Combination Chemotherapy in Non-Small Cell Lung Cancer: A phase II trial

Twenty-six non-small lung cancer patients entered a phase II trial of a 5-drug combination chemotherapy. On day 1, patients received vinblastine, bleomycin, methotrexate, 5-FU, cisplan-tinum, leucovorin, and a similar sequence with an increased dosage was administered on day 6. Out of 22 fully evaluable patients we observed 1 CR and 7 PR. Hematological toxicity was significant, including 15 cases of neutropenia grade 4 and four grade 3, with one death during aplasia. Our results are disappointing but they are similar to most current reports on drug combinations in advanced non-small cell lung cancer. A better scheduling might improve the efficiency toxicity ratio.     

Cisplatin,raltitrexed, levofolinic acid and 5-fluorouracil in locally advanced or metastatic squamous cell carcinoma of the head and neck: a phase II randomized study

BACKGROUND: Cisplatin (CDDP) is among the most active single agents against squamous cell carcinoma of the head and neck (SCCHN), and it is still the reference drug in the induction chemotherapy setting, when used in combination with infusional 5-fluorouracil (5-FU). Raltitrexed has been shown to be devoid of clinical activity against SCCHN when used alone; however, both preclinical and early clinical data regarding the combination raltitrexed-CDDP hold promise. Thymidylate synthase is the target enzyme of both raltitrexed and 5-FU; however, the two drugs have distinct sites of action on the enzyme and the combination of the two agents may be synergistic. We have previously shown that the combination of raltitrexed, levofolinic acid (LFA) and 5-FU has clinical activity against SCCHN; in a subsequent phase I study, cisplatin was added, and the combination of CDDP plus raltitrexed on day 1, followed by LFA and 5-FU on day 2, was judged feasible and active, since a 67% response rate was shown across all dose levels, with a 100% response rate at the recommended dose for phase II. METHODS: Patients with inoperable locally advanced or metastatic SCCHN, not pretreated with chemo- or radiotherapy were randomized to receive either CDDP 60 mg/m2 and raltitrexed 2.5 mg/m2 on day 1 and LFA 250 mg/m2 and 5-FU 900 mg/m2 on day 2 (arm A) or CDDP 65 mg/m2 and methotrexate 500 mg/m2 on day 1, and LFA 250 mg/m2 and 5-FU 800 mg/m2 on day 2 (arm B). Both treatments were repeated every 2 weeks. Evaluation for tumor response was performed after four cycles. According to Simon two-stage design, with a target complete response (CR) rate (p1) of 35%, at least 7 CR among the first 31 treated patients and 16 CR among the final sample size of 52 patients were required. RESULTS: An interim analysis was performed when 36 patients were evaluable in each arm. In arm A, 10 CR (28%) and 19 partial responses (PR) (53%) were observed, for an overall response rate of 81%. In arm B, 3 CR (8%) and 12 PR (34%) were observed, for an overall response rate of 42%. The difference in both CR and overall response rate between the two arms was statistically significant (p = 0.03 and <0.001, respectively). Therefore, the accrual was stopped in arm B and continued only in arm A. Overall, 13 CR (21%) and 34 PR (56%) were observed among the 61 patients who were accrued in arm A, for an overall response rate of 77% (95% confidence interval 64-87%). Neutropenia was the main side effect in both arms (grade 3-4 in 45 and 23 patients in arm A and B, respectively). Extrahematologic toxicity was mild in both arms; however, 2 patients in arm B died due to toxicity (grade 4 mucositis in one case, grade 4 renal toxicity in the other). CONCLUSIONS: Although response data for our experimental treatment look encouraging, the hypothesis of a 35% activity, expressed as capability to induce a CR, cannot be accepted. The results obtained in this study are not substantially different from those of other trials of CDDP-5-FU-based regimens, and our combination is unlikely to represent a major breakthrough when used in this setting.     

Combination therapy with S-1 and CDDP for head and neck cancer

The combination with cisplatin (CDDP) and 5-FU is considered the first choice chemotherapy for squamous cell carcinoma of the head and neck (HNSCC). S-1, a modulation of tegafur developed in Japan, is an active agent for HNSCC. Some clinical phase I/II studies about the combination with CDDP and S-1 have been reported. The combination showed a good response rate of 67.6% for advanced and recurrent HNSCC in our clinical phase I/II study. The regimens of S-1 combined with carboplatin or nedaplatin have also been reported. Regimens containing S-1 appear to have been effective for HNSCC. Multi-institutional phase II studies with a large sample size are needed in the future. The compliance for patients is better than a 5-FU injection because S-1 is orally administrated. The adverse effect, especially for bone mallow toxicity, is equal or upgraded compared with a 5-FU injection. The efficacy and adverse effects of CDDP plus S-1 should be studied in carefully designed phase II/III trials. S-1 will be one of the key drugs for HNSCC in the future.     

A case of advanced gastric cancer that responded to docetaxel with low-dose 5-FU and cisplatin combination chemotherapy after becoming chemoresistant to M-FLP

We report a case of advanced gastric cancer that responded to docetaxel with low-dose 5-FU and cisplatin combination chemotherapy after becoming chemoresistant to M-FLP. A 52-year-old male was diagnosed with type 3 gastric cancer of angulus (poorly differentiated adenocarcinoma) with left neck, Virchow, mediastinal and abdominal lymph nodes metastases. The patient was treated with 5 courses of M-FLP (MTX + 5-FU + LV + CDDP), and the effect of this therapy was PR, but the tumor was chemoresistant to the sixth course of this therapy. After 7 courses of M-FLP, docetaxel (TXT) with low-dose FP (5-FU + CDDP) was administered to the patient as second-line chemotherapy. After 2 courses of TXT with low-dose FP, the gastric cancer and metastatic lymph nodes were remarkably reduced and the effect of this therapy was PR. The toxic events were anemia (grade 2) and leukopenia (grade 3), which were treated with G-CSF. CDDP and 5-FU based regimens are considered as the first-line chemotherapy for metastatic advanced gastric cancer in Japan; however, a second-line chemotherapy has not been established. As in this case, a TXT based regimen is effective and well tolerated therapy as a second-line chemotherapy for metastatic gastric cancer after prior exposure to CDDP and 5-FU.     

Phase II study of the modified regimen of etoposide, leucovorin and 5-fluorouracil for patients with advanced gastric cancer

BACKGROUND: The efficacy of the treatment of advanced gastric cancer is not very good. The response rate to the original etoposide--leucovorin--5-fluorouracil (ELF) treatment is 53% with tolerable side effects. Whether increasing the dose intensity by prolonging the duration of infusion with 5-fluorouracil (5-FU) and leucovorin (LV) from 3 to 5 days for advanced or metastatic gastric cancer patients would enhance the efficacy but not increase side effects is still unknown. METHODS: Thirty-six advanced or metastatic gastric cancer and chemotherapy-naive patients with measurable or evaluable diseases were scheduled to receive intravenous etoposide 100 mg/m2/day on days 2-4, LV 300 mg/m2/day intravenously and 5-FU 500 mg/m2/day intravenously on days 1-5, every 4 weeks. All patients who received at least two courses of chemotherapy were evaluated for tumor response, survival and response duration and toxicity according to the WHO criteria. RESULTS: Thirteen patients showed a response, including five with complete response (CR). The overall response rate was 36% (95% confidence interval, CI, 20-52%) in the whole group and 46% (95% CI 28-66%) in the 28 patients with measurable disease. The median progression-free interval and overall median survival time were 5 and 7 months, respectively. The most frequent toxicity was alopecia (grade I/II 56.3%). The incidence of grade III or greater myelosuppression was 5.9%. No treatment-related death occurred. CONCLUSIONS: The efficacy of the modified ELF by increasing the dosages of 5-FU and LV is not superior to the results of the original regimen, yet it is a relatively safe and tolerable combination regimen for advanced gastric cancer.      

A randomized trial between two neoadjuvant chemotherapy protocols: CDDP + 5-FU versus CDDP + VP16 in advanced cancer of the head and neck

We investigated a phase III randomized trial to compare efficacy and tolerance of CDDP + 5-FU to CDDP + VP16, both given intravenously in patients with unresectable advanced head and neck cancer. The 197 eligible patients were paired off successively on the basis of tumor sites and UICC stage. Comparisons were made through sequential closed plans. In 179 patients, tumor beds and cervical lymph nodes were irradiated, and 20 patients underwent salvage surgical procedures. Cisplatin plus 5-fluorouracil showed a response (CR + PR) rate of 15% greater than that observed with cisplatin plus etoposide (alpha=0.05, power 70%). Complete responses played a major role in the CDDP + 5-FU regimen. Furthermore, we noted a higher cervical node regression with this chemotherapy combination. Because radiotherapy was administered after chemotherapy, we could not analyze the mean duration response for each protocol. No significant difference in survival existed between the two groups. Myelosuppression was the most frequent sign of toxicity observed, especially with the CDDP + VP16 regimen. Mucositis was rare with allopurinol protection. In the CDDP + 5-FU group, one patient had grade 4 cardiac dysfunction, and 3 patients exhibited unconsciousness that may be related to cerebral vascular damage. Thirteen patients died, with 8 cases related to septic shock (5 CPPP + VP16 and 3 CDDP + 5-FU). Cisplatin plus 5-FU chemotherapy showed a satisfactory efficacy and acceptable toxicity profile compared with CDDP + VP16, with caution to patients with a cardiac or vascular history. Although we could not show a benefit in survival with the CDDP + 5-FU protocol, this trial supports literature data and confirms that this regimen may be proposed as a first-line therapy in advanced cancer of the head and neck.     

Neoadjuvant intraarterial chemotherapy with nedaplatin,peplomycin and mitomycin C for advanced cervical cancer

The aim of the present study was to examine the usefulness of neoadjuvant intraarterial chemotherapy (NAC) using nedaplatin as key drug to improve the prognosis in case of advanced cervical cancer. Twenty-five cases of advanced cervical cancer (15 cases of stage II with high risks, 10 of stage III, referred to as the 254-S group) treated by NAC using nedaplatin, mitomycin C and peplomycin were compared with 30 cases (22 cases of stage II with high risks, 8 of stage III, referred to as the CDDP group) treated using cisplatin and mitomycin C which is the conventional regimen, in terms of measurable response, pathological response, rate of lymph node metastasis, cumulative survival rate, side effects and relapse style. According to the evaluation by measurable responses, the response rate was 90% (CR 52%) in the 254-S group and 75% (CR 15%) in the CDDP group. For pathological response of the specimen, the CR rate was 16% in the 254-S group and 23% in the CDDP group. The rate of lymph node metastasis extracted surgically was 33% and 41%, respectively. The cumulative survival rate in the 254-S group was about 10% better than in the CDDP group, but no significant difference was found. Leucopenia of both groups was of the same grade. In the 254-S group, although thrombocytopenia was more critical than in the CDDP group, there was a slight tendency to kidney toxicity. The locoregional recurrence rate was 12% in the 254-S group and 30% in the CDDP group. The distant metastasis rate was 16% and 27%, respectively. Although neoadjuvant intraarterial chemotherapy using nedaplatin as a key drug was useful to improve the prognosis of advanced cervical cancer, measures against recurrence outside the pelvis and individualization of medical treatment were considered to lead to a further improvement of the prognosis.     

Combined MTX.5-FU.CDGP for the treatment of head and neck cancer

Combination chemotherapy including 5-fluorouracil (5-FU) and nedaplatin (CDGP) with methotrexate (MTX) and leucovorin (LV) was administered for modulation in patients with head and neck cancer. We treated 19 patients with MTX.5-FU.CDGP consisting of 150 mg/body of MTX on day 1 followed by a 3-day continuous infusion of 5-FU at 3,500 mg/m2 and 17 injections of LV at 15 mg and infusion of CDGP at 100 mg/m2. Six patients had recurrent head and neck cancer, and 13 had newly diagnosed disease. Eleven of the new patients were concurrently treated with radiation therapy. Treatment-associated toxicity was significant, including mucositis and myelosuppression, but acceptable. Sixteen patients were eligible for evaluation of response. The overall complete response rate was 75.0% (12/16). Patients treated with radiotherapy had a 90.0% (9/10) overall complete response rate.     

A case of gastric cancer with paraaortic lymph node metastasis responding to preoperative chemotherapy and surviving 4 years and 4 months after total gastrectomy

A 68-year-old woman was admitted to our hospital because of type 4 gastric cancer associated with paraaortic lymph node metastasis. Considered surgically incurable, she was placed on preoperative chemotherapy consisting of Methotrexate (MTX) 50 mg (day 1), CDDP 10 mg (day 2-6), 5-FU 500 mg (day 1-6) and Leucovorin (LV) 60 mg (day 2-6). Because of severe nausea and leucopenia, she could receive only 1 course of the chemotherapy. CT on January 7, 1997 (5 weeks after the chemotherapy) showed that the gastric wall thickness and the paraaortic lymph nodes swelling had decreased remarkably. She underwent total gastrectomy on January 13, 1997 (pT2, pN2, pM1 (LYM), stage IV, TNM classification). As an outpatient, she was treated with UFT-E 300 mg/day (continuous until the present) and MTX 50 mg (day 1), 5-FU 500 mg (day 1) and LV 60 mg (day 2-3) once two weeks (total 27 cycles). Four years and 4 months after surgery, although peritoneal recurrence was suspected, she has been managed at our outpatient clinic.     

Bolus and infusional 5-fluorouracil combined with cisplatin in advanced gastric cancer

5-Fluorouracil (5-FU) is the main drug used in the treatment of advanced gastric cancer. Combination chemotherapy is not always superior to 5-FU alone, especially when biomodulators are also administered. In an attempt to exploit all the cytotoxic mechanisms of 5-FU, we carried out a pilot study with a double route of administration of 5-FU (intravenous bolus and continuous infusion) and a multiple modulation of 5-FU by methotrexate (MTX), 6S-leucovorin (6S-LV) and cisplatin (CDDP). A group of 30 patients affected by advanced gastric cancer was treated with MTX 50 mg/m2 and 5-FU 400 mg/m2 as an i.v. bolus on day 1, followed by a 5 day i. v. continuous infusion of 5-FU 600 mg/m2/day and 6S-LV 100 mg/m2/day; on day 3 CDDP 100 mg/m2 was also administered. The regimen was repeated every 4 weeks. Six partial responses (20+/-14. 3%), 12 stable diseases (40+/-17.5%) and 12 progression (40+/-17.5%) were observed in an intent-to-treat analysis. Median survival was 7 months. All responding patients had performance status 0-1. Grade 3-4 toxicity was mainly gastrointestinal, but grade 3-4 anemia and leucopenia were also recorded. The schedule has low activity. The use of different modulators and way of administration of 5-FU does not provide advantages in advanced gastric cancer.     

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.     

Infusional 5-fluorouracil and cisplatin as first-line chemotherapy in patients with carcinoma of unknown primary site

A combination chemotherapy of 5-fluorouracil (5-FU) and cisplatin (CDDP) has demonstrated activities in various malignancies, including head and neck, lung, esophageal, gastric, and pancreatic cancers. We reviewed our experience of 11 patients diagnosed as carcinoma of unknown primary site (CUPS), who were treated with infusional 5-FU and CDDP between January 1998 and December 2005. The median number of cycles administered was three (range: 1-12). All patients had measurable disease. Six partial responses were obtained (response rate: 54.5%, 95% confidence interval: 23.4-83.3%). The median survival time for all patients was 10 mo (range, 2-37 mo). The median time to disease progression was 3 mo (range, 1-6 mo). This regimen was well tolerated, with grade 3-4 neutropenia (two patients), febrile neutropenia (one patient), grade 3 nausea/vomiting (one patient), and grade 3 stomatitis (two patients). Grade 2 leukoencephalopathy was observed in one patient. No treatment-related death was observed. The combination chemotherapy of infusional 5-FU and CDDP was feasible and tolerated with promising activity for CUPS.     

Effect of a 3-hour interval between methotrexate and 5-fluorouracil in the treatment of metastatic colorectal cancer

OBJECTIVE: This phase II study was designed to evaluate the efficacy and toxicity of 3-h interval sequential methotrexate (MTX) and 5-fluorouracil (5-FU) with leucovorin (LV) rescue in the treatment of patients with metastatic colorectal cancer. METHODS: Forty-two patients with histologically confirmed metastatic colorectal cancer and at least one two-dimensionally measurable lesion, aged 30-74 years old, with performance status < or =2 and no or one prior chemotherapy were selected. Patients received sequential MTX 100 mg/m2 by bolus injection and 5-FU 600 mg/m2 at 3 h followed by LV rescue initiated after 24 h (15 mg per body every 6 h for six doses). The treatment was repeated every week or every 2 weeks until disease progression. All patients were treated as out-patients unless complications arose. RESULTS: All 42 patients entered in this study were assessable both for response and toxicity. Fifteen patients achieved objective responses (one complete and 14 partial), for an overall response rate of 36% (95% CI: 11-51%). Response rates in pretreated patients and patients with naive chemotherapy were 27 and 42%, respectively. Sixteen patients had stable disease and 11 progressed with therapy. The median survival for all patients was 378 days. The hematological toxicity was mild with no grade 3/4 leukopenia. The major non-hematological toxicity was diarrhea (one grade 4, four grade 3). CONCLUSIONS: This 3-h interval sequential MTX and 5-FU with LV rescue is an active regimen in patients with metastatic colorectal cancer. The treatment showed mild toxicity and was administered on an out-patient basis. The present findings suggest that this regimen warrants further investigation in patients with metastatic colorectal cancer.     

Preliminary evaluation of chemotherapy with docetaxel, 5-FU, CDDP for recurrent esophageal cancer--a pilot study

A pilot study has been conducted since January 2002 to investigate whether chemotherapy with docetaxel, 5-FU, CDDP could be an effective regimen for recurrent esophageal cancer. Ten patients with recurrent esophageal cancer were treated with the combination of docetaxel 60 mg/m2 (day 1), CDDP 10 mg/body (days 1-5) and 5-FU 500 mg/body (days 1-5) at intervals of 2-3 weeks. All patients had undergone surgery, had a recurrent tumor and had already been treated with chemo-radiotherapy or chemotherapy with CDDP + 5-FU. Response evaluation in 10 patients with measurable disease: partial response 4 patients, stable disease 2 patients and progressive disease 4 patients. The main NCI-CT grade 3/4 toxicity was leukopenia (8/10). Mild to moderate nausea (> or = grade 2) occurred in 3/10 patients.     

Chemotherapy of invasive bladder cancer

This article is a review of the results of systemic chemotherapy for invasive bladder cancer. Transitional cell carcinoma of the urinary tract including the urinary bladder, renal pelvis and ureter has been moderately responsive to chemotherapy. Many chemotherapeutic agents have been studied singly or in combination. Until about 10 years ago, adriamycin (ADM) was the most studied agent for treatment of invasive bladder cancer. However, the results of single agents and combination with ADM have been disappointing; the overall response rate was approximately 20%. With the introduction of cisplatin (CDDP), the efficacy of chemotherapy for invasive bladder cancer has improved significantly. As single agents, CDDP has a response rate of 30 % in 320 cases, methotrexate (MTX), 29% in 236 cases, ADM, 17% in 248 cases, vinblastine (VBL), 16% in 38 cases, and mitomycin C, 13% in 42 cases. Presently the most important agents in the treatment of this disease are CDDP and MTX, and the next most useful agents are ADM and VBL. Recent data from limited trials in patients with advanced bladder cancer suggest that combination chemotherapy regimens with these agents induces a high percentage of complete remissions (CR), an overall response rate between 50% and 70%, and a median response duration of longer than 6 months. Most active combination regimens are M-VAC (CDDP + MTX + ADM + VBL), CMV (CDDP + MTX + VBL), CM (CDDP + MTX) and CISCA (CDDP + ADM + cyclophosphamide). These combination regimens with M-VAC, CMV, CM and CISCA show a response rate of 57%, 57%, 46% and 46%, respectively. However, these drugs have a substantial toxicity and their combination has still been regarded as too hazardous. The attainment of CR in 20% to 40% of cases given these combination regimens has led to adjuvant and neoadjuvant chemotherapy.