Phase II study of hepatic artery infusion with 5-fluorouracil,adriamycin, and mitomycin C (FAM) in liver metastases from colorectal carcinoma

Summary Twenty-seven patients with liver metastases from colorectal carcinoma were treated with 5-fluorouracil, adriamycin, and mitomycin C (FAM) by hepatic artery infusion (HAI) every 2–3 months for a maximum of eight courses. Median survival for all patients was 22 months. Toxicity was acceptable and consisted in severe myelosuppression (8%), duodenal ulceration (8%), moderate nausea and vomiting (50%), and alopecia (100%). HAI with FAM is feasible and may have an impact on survival. Further studies are needed to determine the role of HAI, which may be of potential benefit to a substantial number of patients with metastatic colorectal carcinoma.Presented at the EORTC symposium on treatment of advanced gastrointestinal cancer, Padua, Italy, 1983     

Treatment of advanced gastric carcinoma with 5-fluorouracil adriamycin,and mitomycin C (FAM)

Summary Thirty-three evaluable patients with advanced gastric adenocarcinoma were treated with a combination of 5-fluorouracil, adriamycin, and mitomycin C (FAM). Two complete and five partial remissions (21% response rate) were observed. The overall median survival of all 33 patients was 5.9 months. Responding patients had significantly better survival than the non-responders (P<0.02). Analysis of the results according to sex, pretreatment performance status, and the histologic differentiation of the tumor failed to demonstrate that any of these factors influenced therapeutic results. The low response rate to FAM found in this study might be related to the fact that in the majority of the patients (85%) the primary gastric tumor had not been resected. The side-effects of this regimen were moderate. Taking into account the low response rate and the moderate myelotoxicity observed, a more intensive use of these three drugs in combination is suggested.     

A multicentre, randomised phase III trial comparing protracted venous infusion (PVI) 5-fluorouracil (5-FU) with PVI 5-FU plus mitomycin C in patients with inoperable oesophago-gastric cancer.

BACKGROUND: This randomised study compared protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin C (MMC) in patients with advanced oesophago-gastric cancer. PATIENTS AND METHODS: Two hundred and fifty-four patients with adenocarcinoma, squamous cell carcinoma or undifferentiated carcinoma involving the oesophagus, oesophago-gastric junction or the stomach were randomised. The major end points were tumour response, survival, toxicity and quality of life. RESULTS: The median age of patients treated was 72 years and the two arms were well-balanced for baseline demographic factors. The overall response rate was 16.1% [95% confidence interval (CI) 9.5% to 22.7%] in patients treated with PVI 5-FU alone compared with 19.1% (95% CI 12.0% to 26.0%) for those treated with PVI 5-FU plus MMC (P = 0.555). Median time to treatment failure was 3.9 months for PVI 5-FU and 3.8 months for PVI 5-FU plus MMC (P = 0.195). Median survival was 6.3 months for PVI 5-FU and 5.3 months for PVI 5-FU plus MMC (P = 1.0).Toxicity was mild for both treatments. Symptomatic benefit measured by improvement in pain control, weight loss, dysphagia and oesophageal reflux was observed in over 64% of patients in each arm. Quality of life scores were comparable in each arm. CONCLUSIONS: PVI 5-FU is a safe, effective form of palliation for patients with advanced oesophago-gastric cancer although the addition of MMC adds little extra benefit.     

5-Fluorouracil, adriamycin, and mitomycin C (FAM) combination chemotherapy in adenocarcinoma of the parotid gland

An adenocarcinoma of the parotid gland is a rare tumor and little is known about the efficacy of chemotherapy as a method of treatment. Four patients with a metastatic, or recurrent adenocarcinoma of the parotid gland were treated with a combination chemotherapy consisting of 5-fluorouracil, adriamycin, and mitomycin C (FAM): 5-fluorouracil 330-500 mg/m2, d1-3, q3w or tegafur 400-600 mg/m2 p.o. adriamycin 30-40 mg/m2 q3w, and mitomycin C 3-10 mg/m2, q1-2w. One patient with a lung metastasis showed a good partial response lasting for 19 months and another patient who was resistant to CDDP plus the adriamycin combination, having a lymph node, bone, and bone marrow metastases, had a partial response lasting for 31 months. Results have indicated that adriamycin is one of the effective therapeutic drugs and that FAM combination chemotherapy can provide some efficacy against a parotid cancer.     

A phase II study of combined 5-fluorouracil and mitomycin C in advanced breast cancer

In a Phase II study, 50 patients with advanced breast cancer were treated with a combination of 5-fluorouracil (1000 mg/m2 on days 1 and 2) and mitomycin C (6 mg/m2 on day 2) (FuMi regimen). The courses were repeated every third to sixth week. Although 35 patients had previously received combination chemotherapy and 40 patients had received endocrine treatment, objective responses were obtained in 29 patients (six complete, 23 partial). The survival was significantly correlated to the response (P less than 0.001, log rank test) complete versus partial response, partial response versus no change, no change versus progressive disease. The regimen was well tolerated (19 of 50 experienced nausea). Thirteen patients had hematopoietic toxicity at the day of starting a new course and in six cases, the FuMi regimen had to be discontinued because of longlasting thrombocytopenia. Otherwise, no side-effect of clinical importance was observed. The FuMi regimen is now compared with Adriamycin regimens and can be recommended for both first line chemotherapy and salvage chemotherapy.     

Prospective randomized trial comparing modified FAM (5-fluorouracil (5-FU) + adriamycin + mitomycin C) versus 5-FU alone for the treatment of non-resectable pancreatic and biliary tract carcinomas (the 1st trial in non-resectable patients). Study Group of Surgical Adjuvant Therapy for Carcinomas of the Pancreas and Biliary Tract]

The modified FAM (5-fluorouracil (5-FU) + adriamycin (ADR) + mitomycin C (MMC)) therapy (FAM group) was compared with 5-FU mono-therapy (F group) by multi-institutional randomized trial in the patients with cancer of the pancreas or the biliary tract who underwent non-resection. The patients in FAM group received 6 mg/m2 of i.v. MMC during operation, 310 mg/m2 of i.v. 5-FU for 5 days in the 1st and 3rd postoperative weeks and 12 mg/m2 of i.v. ADR in the 2nd postoperative week. Those in F group received only 5-FU course in the administration schedule of FAM group. Among the cases which completed respective whole administration schedules. 35 cases in FAM group and 36 in F group, better effect than partial response (PR) was observed in neither groups, and there was no significant difference between groups with respect to overall/each disease survival duration, progression-suppressed duration and clinical effect. Primary adverse effects were alimentary symptoms and hepatic dysfunction, neither of which was serious, and there was no difference between groups except that hair loss was observed in more cases in FAM group (p less than 0.05). Results in FAM group did not statistically surpass those in F group, but a tendency was observed that FAM group was better than F group in terms of survival duration and clinical effect for cancer of the gall-bladder.     

Therapy of liver tumors metastatic from colorectal cancer with whole-liver radiation combined with 5-FU,adriamycin, and methotrexate

Summary To determine the relationship between 5-fluorouracil (FUra) toxicity and its RNA- and DNA-directed actions we examined the ability of continuous SC infusion with uridine (Urd), thymidine (dThd), or deoxyuridine (dUrd) to rescue mice from the lethal toxicity of FUra. Male B6D2F₁ mice were treated with a single IP injection of FUra (800 mg/kg) followed in 24 h by a 5-day infusion with either 0.9% NaCl or Urd (0.1, 1, 5, or 10 g/kg/day). Survivors were then followed up for 30 days after FUra treatment. Urd (1, 5, or 10 g/kg/day) rescued mice from the lethal toxicity of FUra, whereas Urd (0.1 g/kg/day) was as ineffective as 0.9% NaCl as a rescue agent. With variable doses of FUra followed in 24 h by a Urd infusion (5 g/kg/day) for 5 days, Urd rescued mice treated with FUra (400, 600, or 800 mg/kg) but was ineffective against higher doses of FUra (1,000 or 1,200 mg/kg). Mice treated with FUra (800 mg/kg) followed in 24 h by a 5-day infusion with either dThd (1, 5, or 10 g/kg/day) or dUrd (1 or 5 g/kg/day) could not be rescued from the lethal toxicity of FUra. In all experiments deaths occurred between 6 and 12 days after FUra. These results, which demonstrate a specificity for Urd, but not for either dThd or dUrd, for rescuing mice from the lethal toxicity of FUra, suggest the importance of the RNA- rather than the DNA-directed actions of FUra as a determinant of its toxicity in mice.     

Cyclophosphamide, methotrexate,5-fluorouracil, alternating with adriamycin and mitomycin C in metastatic breast cancer: a pilot study

To explore the clinical applicability of the Goldie and Coldman hypothesis, we treated 28 patients with metastatic breast cancer with alternating non-cross-resistant chemotherapy. The patients received cyclophosphamide, 600 mg/m2, 5-fluorouracil, 600 mg/m2, methotrexate, 40 mg/m2, alternated every three weeks with adriamycin, 60 mg/m2, and mitomycin C, 10 mg/m2. Only one patient had previously received palliative chemotherapy. Six patients had received adjuvant CMF, and 17 patients had been pretreated with endocrine therapy (13 for advanced disease, 4 as adjuvant). Fourteen patients had bone involvement, and 10 had visceral metastases. A mean of 12 cycles was given to 24 evaluable patients. The objective response rate was 67%: 11 patients (46%) achieved complete and 5 (21%) partial remission. Response rate in soft tissues was 83.3%, in bone 50%, in liver 100%, and in lung 80%. The median duration of response was 14 months, with 7 patients still in remission. No life-threatening toxicity was observed. Our preliminary results support the validity of this approach and the efficacy of this combination chemotherapy. A large-scale randomized study is warranted.     

Vinorelbine, cisplatin and continuous infusion of 5-fluorouracil (ViFuP) in metastatic breast cancer patients: A phase II study

Purpose:Chemotherapy regimens for patients with advanced breastcancer or large primary tumours (including locally advanced disease) usuallycontain anthracyclines, taxanes or both. We investigated a multi-agent regimenfor patients for whom anthracyclines and/or taxanes may not be suitable. Weassessed efficacy in terms of response rate and time to progression of acombination with continuous infusion 5-fluorouracil (5-FU), vinorelbine andcisplatin (ViFuP regimen), as a first or subsequent line treatment formetastatic breast cancer patients. Patients and methods:One hundred consecutive patients withadvanced breast cancer were treated with 5-FU 200 mg/m²administered continuously through a permanent central venous line; vinorelbinewas given on days 1 and 3 at a dose of 20 mg and cisplatin was administeredat 60 mg/m² on day one. Therapy was given every three weeks. Themedian age was 50 years (range 23–72). Fifty-two patients had receivedprior chemotherapy for metastatic breast cancer, and sixty-one percent hadpreviously received anthracyclines, thirty-five percent taxanes andtwenty-nine percent 5-FU as a bolus injection. All patients were assessablefor toxicity, four patients were not assessable for response. Results:There were four complete responses (4%).Forty-nine patients had a partial response (overall response rate, 55%;95% confidence interval (CI): 45%–65%). After amedian follow-up of 10.2 months, median duration of response is 5.2 months(range 1.5–20.7+ months), time to progression (TTP) is 6.8 months (range0.3–24.7 months). Acute toxicity, including myelosuppression, was mild:only 18% of patients had grade 4 granulocytopenia and one patientexperienced grade 4 diarrhea. Only 15% of patients had anynon-hematological grade 3 toxicity including nausea (4%), stomatitis(4%), diarrhea (2%), fatigue (1%), fever (1%),photosensitivity (1%), hand–foot syndrome (1%). Grade 2alopecia was observed only in six patients (6%). Eleven patientsdeveloped a right diaphragmatic supra elevation, while deep vein thrombosis,central venous catheter associated, occurred in eight patients. Conclusions:We identified a combination chemotherapy withnoteworthy efficacy and well tolerated subjectively as either a first- orsecond-line treatment for metastatic breast cancer patients. The regimenwarrants further development focusing on the comparison with either continuousadministration of oral fluoropyrimidine derivatives.     

Multicenter randomized phase III trial comparing protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin in inoperable pancreatic cancer.

PURPOSE: To compare protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin (MMC) in patients with advanced pancreatic cancer in a multicenter, prospectively randomized study. PATIENTS AND METHODS: Two hundred eight patients were randomized to PVI 5-FU (300 mg/m(2)/d for a maximum of 24 weeks) or PVI 5-FU plus MMC (7 mg/m(2) every 6 weeks for four courses). The major end points were tumor response, survival, toxicity, and quality of life (QOL). RESULTS: The two treatment groups were balanced for baseline demographic factors, and 62% had metastatic disease. The overall response rate was 8.4% (95% confidence interval [CI]) 3.2% to 13.7% for patients treated with PVI 5-FU alone compared with 17.6%; 95% CI 10.3% to 25.1% for PVI 5-FU plus MMC (P =.04). Median failure-free survival was 2.8 months for PVI 5-FU and 3.8 months for PVI 5-FU plus MMC (P =.14). Median survival was 5.1 months for PVI 5-FU and 6.5 months for PVI 5-FU plus MMC (P =.34). Toxicities in both arms were mild. There was an increased incidence of neutropenia in the 5-FU plus MMC arm (P <.01), although no differences in infection were seen. No patients developed hemolytic uremic syndrome. Global QOL improved significantly after 24 weeks of treatment compared with baseline for patients receiving 5-FU plus MMC, although there was no statistically significant difference in QOL between arms. CONCLUSION: PVI 5-FU plus MMC resulted in a superior response rate in comparison with PVI 5-FU alone in advanced pancreatic cancer, but this did not translate into a survival advantage. These results emphasize the importance of chemotherapy in this setting and the continuing value of the fluoropyrimidines in pancreatic cancer.     

Chemotherapy for advanced pancreatic cancer. A comparison of 5-fluorouracil, adriamycin, and mitomycin (FAM) with 5-fluorouracil, streptozotocin, and mitomycin (FSM)

One hundred ninety-six patients with advanced pancreatic cancer were randomized to receive one of two combination chemotherapy programs: FAM (5-fluorouracil, Adriamycin [doxorubicin], mitomycin) or FSM (5-fluorouracil, streptozotocin, mitomycin). Patient characteristics were comparable in both groups. Overall response rates for those with measurable disease (14% on FAM, 4% on FSM) were not significantly different (P = 0.07). There was no significant difference in overall survival between patients treated with FAM and FSM (median survivals of 26 and 18 weeks, respectively). Survival benefits of FAM were significant only for patients with measurable disease. Toxicity of both regimens was acceptable and comparable, aside from greater renal toxicity and more nausea and vomiting with FSM. The results failed to confirm the 35% to 40% response rates previously reported for FAM and FSM in advanced pancreatic cancer.     

A five-year-survival case in which complete response was recognized after combined chemotherapy using 5-fluorouracil, adriamycin and mitomycin C (FAM) for unresectable gastric cancer]

FAM (5-fluorouracil, adriamycin, mitomycin C) therapy was performed on a 65-year-old man with unresectable gastric cancer. Cancer cells have not been recognized by endoscopic biopsy after the patient's complete response. He is alive without metastasis of recurrence for five years.     

Optimisation of irinotecan dose in the treatment of patients with metastatic colorectal cancer after 5-FU failure: results from a multinational, randomised phase II study

Although irinotecan 350 mg m(-2) is a standard option for relapsed/refractory advanced colorectal cancer, there is some evidence that suggests that a higher dose may be more effective, with acceptable tolerability, following 5-fluorouracil (5-FU). This study assessed the optimal dosing strategy for irinotecan, along with treatment efficacy and safety. A total of 164 patients with metastatic colorectal cancer progressing after failure on 5-FU or raltitrexed received either 350 mg m(-2) irinotecan (Group A; n=36) or 250, 350 or 500 mg m(-2), according to individual patient tolerance (Group B; n=62) or based on risk factor optimisation (Group C; n=66). There were no complete responses. There was a trend towards a higher overall response rate in Group B (13%) than in Groups A (8%) and C (9%). Tumour control growth rate was high in all three groups: 58% in group A, 60% in Group B and 50% in Group C. A total of 34% of patients in Group B and 9% in Group C were able to receive a dose of 500 mg m(-2). Median duration of response and time to progression were significantly longer in Groups A and B compared with Group C. No significant between-group differences for any adverse events were seen, although there was a small trend towards better tolerability in Group B. Individual dose escalation based on patient tolerance may allow more patients to receive a higher irinotecan dose without causing additional toxicity and can be an appropriate patient management strategy.     

Combination chemotherapy of 5-fluorouracil (5-FU), adriamycin (ADM), cis-diamminedichloroplatinum (II) (CDDP) and mitomycin C (MMC) (FAP.MMC) in advanced gastric cancer

Twenty patients with advanced gastric cancer were treated with FAP.MMC (5-FU 350 mg/m2 i.v. on days 1-3, ADM 40 mg/m2 i.v. on day 1, CDDP 20 mg/m2 i.v. on days 1-3, MMC 6 mg/m2 i.v. on day 1), administering 5-FU, ADM and CDDP every 4 weeks and MMC every 8 weeks. Fourteen patients were evaluable for responses. Four (29%) partial responses and two minor responses were observed. The median duration of partial response was 3.8 months (range 2.5-7 months). The median overall survival time was 5 months (range 1.5-15 months). Leukopenia was relatively severe, with a median WBC nadir of 1,300/mm3. Nausea and vomiting were frequent but moderate. However, these toxicities were clinically manageable. FAP.MMC was thus considered effective for advanced gastric cancer.     

Phase I/II study of irinotecan, UFT and leucovorin with hepatic arterial infusion using 5-FU in colorectal cancer patients with unresectable liver metastases

Purpose

To evaluate the efficacy and tolerability of systemic chemotherapy with irinotecan (CPT-11), UFT and leucovorin (LV) combined with hepatic arterial infusion (HAI) consisting of 5-fluorouracil (5-FU) in colorectal cancer patients with unresectable liver metastases.

Methods

Patients were treated concurrently with escalating doses of intravenous CPT-11 (100, 120, and 140?mg/m²) on day 1 of each 14-day treatment cycle, with oral UFT (300?mg/m² per day) and LV (75?mg/body per day) on days 1?C7 of each cycle, and with HAI 5-FU (2,000?mg/week) on days 8?C14 of each cycle.

Results

Twelve patients were enrolled in the phase I study. The maximum-tolerated dose was not reached. Consequently, the recommended dose of CPT-11 for the phase II study was determined to be 140?mg/m². Twenty-two patients were evaluated in the phase II study. Five patients experienced grade 3 neutropenia, two experienced grade 3 anorexia, two experienced nausea, and two experienced vomiting. An overall response was observed in 19 out of 22 patients (86.4%). The median progression-free survival period was 11.2?months, and the 3-year survival rate was 50.6%. Fourteen patients (63.6%) were ultimately able to undergo a complete liver resection.

Conclusions

Chemotherapy with CPT-11 and UFT/LV combined with HAI yielded a high response rate and enabled a significant proportion of patients with initially unresectable liver metastases to undergo surgical resection. Further trials are warranted.     

A phase II study of UFT and Leucovorin in combination with mitomycin C in patients with metastatic colorectal cancer

The main objectives of this phase II study were to determine efficacy and safety of the combination of UFT with Leucovorin and mitomycin C in patients with metastatic colorectal cancer. Ninety-seven patients were treated with UFT (91 patients 300 mg/m², 6 patients 250 mg/m²)+Leucovorin 90 mg days 1-28 q 5 weeks. During the first 4 cycles the patients also received mitomycin C 7 mg/m² on day 1. At the end of 4 courses patients with benefit from the treatment could receive further courses of UFT and Leucovorin alone. Two patients had a complete response (2%), 20 (21%) had a partial response, 40 (41%) had no change, 19 (20%) had progression, and 16 (17%) were not evaluable for response. The overall response rate by intention to treat was 22/97 (23%). Median time to progression was 5 months and median survival 13 months. Severe (grade 3-4) toxicities included: anorexia 3%, nausea 6%, vomiting 7%, diarrhoea 7%, and fatigue 9%. Febrile neutropenia, renal failure, and thrombocytopenia were seen in 1% of the patients, respectively. The combination of UFT with Leucovorin and mitomycin C shows similar clinical activity with regard to overall response rate (23%) and survival (13 months) to other frontline 5-fluorouracil-based therapies in metastatic colorectal cancer patients. The results indicate that mitomycin C did not increase either efficacy or toxicity. Therefore, phase III trials with this regimen cannot be recommended.     

Individual 5-FU dose adaptation in metastatic colorectal cancer: results of a phase II study using a bimonthly pharmacokinetically intensified LV5FU2 regimen

Aim The aim of this phase II study was to determine the efficacy and tolerability of the bimonthly, pharmacokinetically intensified LV5FU2 regimen in the treatment of metastatic colorectal cancers.Methods A total of 53 patients (23% second-line; 25 male/28 female; mean age 67 years; WHO performance status 0 in 38, 1 in 10 and 2 in 5) were treated in cycle 1 with the standard LV5FU2 regimen (leucovorin 200 mg/m² per day followed by a 5-FU bolus 400 mg/m² per day and a 22-h 5-FU continuous infusion 600 mg/m² per day for two consecutive days every 2 weeks), and the AUC in mg·h/l·m² was calculated. For cycle 2, according to a predefined schedule depending on the cycle-1 AUC value, in the absence of grade 3 toxicity, the 5-FU infusion dose was increased by 150% for AUC 5, by 100% for AUC >5–10, by 50% for AUC >10–15, and by 25% for AUC >15–20. 5-FU plasma concentrations were determined using high-performance liquid chromatography. A Bayesian methodology was used to assess individual pharmacokinetic parameters using the NONMEM computer program.Results Among the 53 eligible patients, 87% (per-protocol population) received an increased dose in cycle 2 and 72% received the same dose. The median relative dose intensity was 1.28 (range 0.5–1.54) compared with the non-adapted theoretical total 5-FU dose. The objective response rate was 37% (95% CI 23–50%) in the intention-to-treat population and 47% (95% CI 29–65%) in the first-line per-protocol population. The median response duration was 10.4 months. The median progression-free survival (PFS) and overall survival (OS) were, respectively, 7 and 18.6 months. PFS and OS in first-line per-protocol patients were, respectively, 9.2 and 20 months. No deaths were attributed to toxicity of 5-FU despite the high doses administered. Of the 53 patients, 19% experienced gastrointestinal and 30% haematological grade 3/4 toxicities. Hand-foot syndrome was common but mild (grade 3 in one patient).Conclusions This strategy could be compared in a phase III trial with the standard LV5FU2 regimen.     

Phase I-II study of hepatic intraarterial one-shot administration of adriamycin in patients with metastatic liver cancer

For the purpose of obtaining the optimal dose of adriamycin (ADM) in hepatic intraarterial one-shot administration, phase I-II study was conducted in 14 patients with various liver cancers. The starting dose of ADM was 20 mg/m2 (4 patients) and the doses were escalated to 40 mg/m2 (5 patients), 60 mg/m2 (4 patients) and 80 mg/m2 (3 patients). One patient with salivary gland cancer showed PR for the liver metastasis. Major toxicity was leukopenia. With a dose of 40 mg/m2, 3 out of 4 patients showed nadir of WBC counts below 4,000/mm3 (2,400, 2,900, 3,100), 60 mg/m2 (1,100, 1,500, 2,200 and 2,700), and 80 mg/m2 (900, 1,200, and 1,400). Nadirs of WBC counts were observed from 9 to 15 days after the one-shot administration, and recovered above 4,000/mm3 in 1 to 3 weeks. Plasma concentrations of ADM from the peripheral vein were determined by HPLC in 12 patients, 14 courses. The curves of ADM plasma levels after 20 and 40 mg/m2 bolus injections were almost the same, and in patients treated with 60 and 80 mg/m2 the curves were also quite similar, but higher in the plasma levels, comparing with in patients with 20 and 40 mg/m2. There might be a limit of ADM tissue absorption, and above the doses 60 mg/m2, ADM might be overflowed, followed by side effects, especially leukopenia. Upon these data of venous plasma concentrations of ADM and leukopenia, the optimal dose of ADM in the hepatic intraarterial one-shot administration seemed to be 40 mg/m2.     

Pilot study of combined treatment with continuous infusion of 5-fluorouracil, mitomycin C, and cisplatin (FMP) in patients with inoperable advanced gastric cancer

We investigated combined chemotherapy with 5-fluorouracil (600 mg/m2/day, day 1-5, c.i.v.), mitomycin-C (6 mg/m2, day 6), and cisplatin (60 mg/m2, day 7) for inoperable advanced gastric cancer, including those with poor performance status (PS). Overall response rates were 62.5% (20/32), 59.1% (12/22) for PS 0-2 and 70.0% (7/10) for PS 3-4. Median survival was 7.2 months, 8.7 for PS 0-2; and 6.3 for PS 3-4. There was no serious toxicity or any treatment-related death. This therapy is useful, even for poor PS.     

Intrahepatic-artery infusion of cis-diamminedichloroplatinum (II) and 5-fluorouracil in primary or metastatic liver cancer

Eight hepatocellular cancer patients and eighteen metastatic liver cancer patients were treated with intrahepato-arterial infusion of CDDP (cis-diamminedichloro-platinum II) plus 5-FU (5-fluorouracil); CDDP (0.8-1.0 mg/kg) was given once every 7 or 10-14 days, while 5-FU (250-100 mg/day) was infused daily. A partial response was obtained in 5 of 8 patients with primary liver cancer and in 9 of 14 evaluable patients with metastatic liver cancer. However, severe complications due to bone marrow suppression were observed in 4 patients, 3 of whom died of septicemia and one of enterocolitis. This combined intra-hepato-arterial chemotherapy exerts a synergistic anticancer effect on malignant liver tumors, although the bone marrow suppression associated with it remains to be overcome.