Successful treatment of pseudomyxoma peritonei using combination chemotherapy of intraperitoneal low-dose CDDP and oral 5'-DFUR administration

We report a case of pseudomyxoma peritonei treated with combination chemotherapy. A 73-year-old woman was diagnosed as having psuedomyxoma peritonei originated from the vermiform appendix. Appendectomy was performed, and 10 mg of MMC was administered intraperitoneally. From day 7, 600 mg/day of 5'-DFUR was orally given for 2 years, and 20 mg of CDDP once a month was intraperitoneally administered seven times. The patient has been doing well with no evidence of tumor recurrence for two years after operation. Combination chemotherapy with CDDP and 5'-DFUR, as a biochemical modulation therapy, has fewer side effects and leads to better quality of life of patients. We recommend a combination chemotherapy with low-dose CDDP and 5'-DFUR for patients in poor general condition.     

Combination therapy with 5'-DFUR, MMC and CDDP in patient with far advanced gastric cancer: report of a case

A 48-year-old man was referred to our hospital for a Borrmann 3 type advanced gastric cancer. Endoscopic biopsy disclosed poorly differentiated adenocarcinoma. Ultrasonography and CT scan revealed left hydronephrosis. Endoscopic retrograde cholangiography detected a stenosis of common bile duct at the hepatic hilum due to lymph nodal metastasis, and laparoscopy revealed peritoneal dissemination. Because the tumor was diagnosed as not for curative resection, the patient was treated by 4 courses of combination therapy with 5'-DFUR, MMC and CDDP. No adverse effect of chemotherapy was observed. As a result, lymph nodal metastasis and peritoneal dissemination were reduced. Curative intent total gastrectomy was performed, together with pancreatico-splenectomy, left hemicolectomy, cholecystectomy, and extended lymph nodal dissection. The patient is well and alive with no sign of recurrence 2 years after operation.     

Combination chemotherapy with 5-FU and CDDP or CDDP analog for head and neck cancer

Combination chemotherapy with CDDP and 5-FU is one of the effective regimens for head and neck cancer. We studied the difference in the effects and adverse effects between two kinds of schedules of CDDP administration for CDDP-5-FU combination chemotherapy. For 13 patients, CDDP was administered on 5 consecutive days from day 1 to day 5 at a daily dose of 16 mg/m2 (Regimen A). For 14 patients CDDP was administered 80 mg on day 1 (Regimen B). 5-FU was administered 700 mg/m2/ day as a continuous drip infusion for 120 hours from day 1 to day 5. For regimen A, the response rate was 77%; for regimen B, it was 64%. The pattern of adverse effects showed a difference. Regimen B was more toxic for renal function than regimen A. But regimen A showed toxicity for bone marrow function. Acute phase nausea and vomit appeared more frequently in regimen B. The difference in the adverse effect pattern, which depends on the schedule of CDDP administration, seems important in order to apply this regimen for head and neck cancer patients safely. The schedule of CDDP administration should be changes depending on the renal and bone marrow function of patients. In order to evaluate the efficacy of UFT as adjuvant chemotherapy, UFT was administered p.o. to patients with maxillary sinus carcinoma for more than one year after definitive treatment with surgery or radiotherapy. Fifteen patients with UFT adjuvant chemotherapy showed significantly better survival rates than patients without adjuvant chemotherapy. We also studied adjuvant chemotherapy with CBDCA and FT for patients with advanced head and neck cancer. Administration with UFT (600 mg/day) from day 1 to day 14 with CBDCA 350 mg/m2 at day 7 was repeated more than twice. This regimen showed low toxicity and better survival for nasopharyngeal cancer patients. More clinical trials with this regimen for adjuvant chemotherapy are needed.     

Results of combination therapy of UFT-E with low-dose CDDP for patients with advanced recurrent breast cancer]

CDDP, as a modulator for 5-FU, has already been described as a very effective treatment for gastrointestinal tract cancer. We administered a dose of 400 mg of UFT-E orally every day, and 10 mg of CDDP by drip infusion twice weekly, for more than 10 weeks to 12 outpatients with metastatic local, pulmonary, hepatic, osteal or multiple-organ cancer which showed a poor response to the pretreatment, and assessed its efficacy and drug toxicity. In terms of the clinical efficacy of this therapy, CR was noted in one patient and PR in 2 patients with a response rate of 25%. The incidence of drug toxicity was low. Complications included temporal transient nausea and anorexia in two patients and leukopenia grade 2 as bone marrow suppression in 3 patients. From the standpoint of QOL, as well as in terms of both antitumor effect and drug toxicity, the therapy mentioned above was believed to be effective for outpatients with advanced recurrent breast cancer.     

Effect of combination chemotherapy of low-dose CDDP. Continuous infusion of 5-FU, and intermittent CPT-11 administration for 2 advanced pancreatic cancer cases with liver metastasis

Nitric oxide slows bone remodeling and bone loss in animals. Because nitroglycerin and other nitrates increase nitric oxide levels, we hypothesized that nitrate use may be associated with greater bone mineral density (BMD) and decreased risk of fracture in humans. Further, intermittent nitrate use may be associated with greater benefits than daily nitrate use, which results in tachyphylaxis. We tested this hypothesis using data from the Study of Osteoporotic Fractures. We prospectively studied 6201 elderly women of whom 317 took nitrates on a daily basis and 74 used them intermittently. We measured BMD at the hip and the heel and adjusted all comparisons for multiple potential confounders. We found that women taking daily nitrates had slightly greater hip BMD (difference, 13%; 95% confidence interval [CI], 0.14-4.1%) but the same heel BMD (difference, 0%; 95% CI -2.6-2.6%) as nonusers. By contrast, women using nitrates intermittently had substantially greater hip (difference, 2.6%; 95% CI, 0.4-6.8%) and heel BMD (difference, 53%; 95% CI, 2.6-11%) than nonusers. This study suggests that the intermittent administration of nitrates may enhance BMD.     

Evaluation of intra-arterial infusion chemotherapy for advanced gastric cancer

We evaluated the therapeutic efficacy of intraarterial infusion chemotherapy in advanced gastric cancer, its side effect and patient prognosis, in comparison with systemic infusion. Of 125 cases of advanced gastric cancer, 41 cases received intraarterial chemotherapy (A group) and the rest were given systemic infusion (S group). Protocols of chemotherapy were 5-FU + MTX in 49 cases, 5-FU + cisplatin in 62, and 5-FU + MMC in 14. Location of the disease was the peritoneum in 69 cases, nodes in 59, liver in 38, and other sites, 33. The response rate of A group was significantly higher than that of S group, at 31% and 13% respectively. Although 41% of cases showed side effects (> or = grade 2), there was no significant difference between the 2 groups. The median survival period and 1-year survival rate were 8.4 months and 35%, respectively, and there was no significant difference between the 2 groups. In cases with liver metastasis, the prognosis of A group was better than that of S group. The results suggest that intra-arterial infusion chemotherapy is an effective treatment for liver metastasis from gastric cancer.     

Intra-arterial chemotherapy to improve quality of life in cases of unresectable advanced or recurrent breast cancer

We performed repetitive intra-arterial infusion chemotherapy (I.A.) with epirubicin in order to improve the quality of life (QOL) in 3 cases with locally advanced or recurrent breast cancer which were diagnosed as surgically unresectable and seemed uncontrollable by outpatient systemic chemotherapy. The patients were admitted to our hospital for chest wall invasion, lymph node metastasis, bleeding, pain, or edema in upper extremity. Therapeutic effects included 1 case of CR and 2 cases of PR in the primary site, and similar effects were obtained in metastasized lymph nodes. We could perform mastectomy in both of the 2 cases with locally advanced cancer after I.A., Although leukocytopenia, which was the dose limiting factor in this regimen, was observed in all 3 cases, it was Grade 2 or 3 and recovered by G-CSF. With regard to their QOL, symptoms which had driven them to inpatient treatment remarkably improved in all of the cases. Thus, after 2 series of I.A. they could receive maintenance systemic chemotherapy as outpatients. Our findings showed that the I.A. as a local control treatment in patients with unresectable advanced or recurrent breast cancer is useful for the improvement of their QOL.     

A case of recurrent breast cancer responding to long-term treatment with 5'-DFUR combined with MPA

A 55-year-old woman with recurrent breast cancer treated with sequential mastectomies, chemo-and hormonal therapy of UFT, CPM and TAM, achieved remission. Six months later she was admitted with a diagnosis of carcinomatous pleurisy. A large pleural effusion was drained followed by administration of ADM, which improved her effusion and accompanying dyspnea. The effusion recurred but the patient desired outpatient treatment. Thus, we prescribed oral 5'-DFUR and MPA. One month later, her cough had improved and her sputum cytology was negative, while on chest radiograph the pleural effusion had decreased and the patch-like shadows in her right lung field had disappeared. She was considered as a case of PR. At one year and 3 months after starting concomitant 5'-DFUR and MPA the pleural effusion disappeared. The patient has received this outpatient treatment for 2 years without adverse reactions.     

A case of recurrent breast cancer responding to combination therapy with mitoxantrone (MIT), 5'-deoxy-5-fluorouridine (5'-DFUR) and medroxyprogesterone acetate (MPA)

The patient was a 50-year-old woman who had undergone left standard radical mastectomy who had undergone left standard radical mastectomy on June 1, 1986. She showed multiple liver metastases with elevation of CEA level in July, 1991, and 5'-DFUR plus MPA combination therapy was started. The daily dosages were: 800 mg/body and 1,200 mg/body, respectively. After intra-arterial infusion of pirarubicin and Lipiodol, bilateral oophorectomy was performed and an implantable reservoir for intra-arterial infusion chemotherapy was implanted via the proper hepatic artery. Then she was treated by arterial-infusion of mitoxantrone 10mg/body intermittently every two weeks. The metastatic foci responded to this therapy and her CEA level decreased.     

Low-dose CDDP and continuous 5-FU treatment of advanced gastric cancer with peritoneal dissemination: a case with long disease-free survival

The patient was diagnosed to have gastric cancer (T3 N3 M0 P3, Stage IV b). We conducted LcFP therapy. CDDP, 7 mg/m2/day, day 1-5 i.v. drip for 2 hours, and 5-FU, 170 mg/m2/day, day 1-7, i.v. continuously for 24 hours. After 3 courses (one course: 4 LcFPs followed by one rest week), down staging (T3 N2 M0 P1. Stage IV a) and improvement of performance status were obtained, and then surgical resection was undertaken. After operation one course of LcFP therapy served as adjuvant chemotherapy. The patient has survived over one year and 8 months to date in a tumor-free condition. LcFP therapy promises to be useful in the clinical management of advanced gastric cancer.     

Preoperative neoadjuvant chemotherapy with a combination of 5-fluorouracil, adriamycin and cisplatin (FAP) for advanced esophageal cancer invading trachea or main bronchus

Conventional irradiation and systemic chemotherapy is scarcely effective for advanced esophageal cancer invading trachea or main bronchus. Therefore, to reduce the area of invasion and suppress distant metastasis, we have preoperatively treated 4 patients suffering from advanced esophageal cancer invading the trachea or main bronchus by neoadjuvant chemotherapy (FAP) as follows: 2 times every 4 weeks, CDDP 100 mg and ADR 50 mg on day 1 and continuous infusion of 5-FU 1,000 mg/day for 7 days. The response rate (PR) was 75% (3/4). In 2 of 4 patients (50%), no cancer cells except broad fibrosis were detected histologically in the region of the trachea or main bronchus suspected to be invaded. There was no severe complication. This FAP regimen is suspected to be useful chemotherapy for advanced esophageal cancer.     

A case of advanced gastric cancer with liver and lung metastasis effectively treated by combined chemo-immunotherapy of MMC, 5'-DFUR, OK-432

A sixty-eight-year-old male patient was diagnosed as having inoperable advanced gastric cancer with liver and lung metastasis. The patient was treated by combined chemo-immunotherapy of MMC 10 mg/M, 5'-DFUR 800 mg/day and OK-432 5 KE/2 W. Six months after commencing chemotherapy, CT-scan and upper GI series revealed that metasized liver tumors and stomach lesion were remarkably decreased in size and no cancer cell was confirmed by endoscopic biopsy. Further, the metastatic lung tumor has disappeared on chest X-ray. The patient had been well without any evidence of tumor re-progression for over one year, but from July the liver tumor began to metastasize again and the patient eventually died of liver metastasis on Jan. 1, 1993.     

Two cases of advanced gastric cancer effectively treated with chemotherapy of 5-fluorouracil, cisplatin and cytarabine

We reported two cases of advanced gastric cancer effectively treated with chemotherapy of 5-fluorouracil (5-FU), cisplatin (CDDP) and cytarabine (Ara-C), 5-FU (300-350 mg/body) was given by continuous intravenous infusion. Ara-C (20-40 mg/body) by continuous infusion and CDDP (15-20 mg/body) were added intravenously for 3-6 days. For case 1, epirubicin (30 mg/body) was also given on the first day of each therapy course. Case 1 was a 62-year-old female who had gastric cancer with liver metastasis, ovarian metastasis and peritonitis carcinomatosa. After 3 courses of the chemotherapy, reduction of ovarian metastasis greater than 75% was observed. The value of CA125 decreased from 6,800 U/ml to 527 U/ml and ascites disappeared. Case 2 was a 54-year-old male who had type 3 advanced gastric cancer with multiple liver metastases. He received 6 courses of the therapy. Both primary and metastatic tumors showed over 50% reduction in tumor size. These suggested that this combination therapy was effective for inoperable advanced gastric cancers.     

Retrospective comparison of infusional 5-fluorouracil, doxorubicin, and mitomycin-C (modified FAM) combination chemotherapy versus palliative therapy in treatment of advanced gastric cancer

About one-third of patients with gastric cancer are unresectable at the time of diagnosis. Their median survival is < 6 months, with a grave prognosis. The purpose of this study was to assess the efficacy of a modified FAM (mFAM) regimen in advanced gastric cancer. We retrospectively reviewed the clinical records of 409 advanced gastric cancer patients who had not received curative surgery. Among 409 patients, 202 patients were treated with an mFAM regimen (infusional 5-FU + doxorubocin + mitomycin-C), and 207 patients received no chemotherapy (control group). No differences were found in clinical parameters between the two groups. The 1-year survival rates were 34.1% for the mFAM-treated group and 22.5% for the control group (p = 0.0135). In subset analysis, a higher 1-year survival rate was demonstrated in patients with mFAM and palliative surgery. Of the 154 evaluable patients in the mFAM-treated group, the response rate was 17.5%. In these patients, median response duration was 30 weeks, and progression-free survival was 23 weeks. Overall toxicity of mFAM regimen was relatively tolerable and reversible. In conclusion, FAM combination chemotherapy, which has been used as a standard therapy, prolonged survival after modification of the administration schedule and combination with palliative surgery. A prospective randomized study is warranted to confirm this conclusion from our retrospective study.     

Hypofractionated radiotherapy with concurrent 5-fluorouracil radiosensitisation for recurrent or locally advanced colorectal cancer. A phase II study

In a pilot study we treated 19 patients suffering from recurrent or locally advanced inoperable colorectal cancer, with concurrent hypofractionated radiotherapy (4-5 Gy/fraction, 2 fractions per week) and 5-fluorouracil bolus, 1 hour before RT at doses of 300 mg/m2. For 16 patients treated with radical intent the Normalised Total Dose for alpha/beta = 10 Gy ranged between 56-74 Gy (median 62 Gy). The schedule used was very well tolerated. Moderate grade II haematological toxicity was observed in 11% of cases and diarrhoea grade II/III resulting in 2-4 weeks treatment delay was observed in 26% of cases. One case with bowel perforation and one with painful subcutaneous fibrosis was observed during 12-27 months of follow-up. Out of 16 patients treated with radical intent 4 (25%) showed complete response and the overall response rate was 56% (9/16). The one-year symptom-free survival was obtained in 11/16 (69%) radically treated patients. It is concluded that hypofractionated radiochemotherapy with 5-fluorouracil for recurrent or locally advanced colorectal cancer is an effective regimen and has acceptable acute and late toxicity. Further investigation is required.     

A case of stage IV breast cancer showing long-term complete response to combination therapy with 5'-DFUR and MPA

We report a 62-year-old woman with supraclavicular lymph node, pleural and bone metastases from breast cancer showing a long-term complete response to combination therapy with 5'-DFUR and MPA. A large amount of pleural effusion was drained followed by administration of ADM, which improved the amount of effusion. Treatment with CAF and TAM decreased tumor size, but CAF was abandoned due to severe leukopenia. Mastectomy was performed for local control. However, levels of tumor markers increased progressively. Administration of CMF was tried, but tumor markers continued to increase. Therefore, combined chemoendocrine therapy with 5'-DFUR and MPA was undertaken. Levels of tumor markers normalized and a complete response was obtained 13 months after starting this combination therapy. There are no further metastatic lesions evident, and this status has been consistently maintained for more than three years (six years and five months after diagnosis of breast cancer). There were no significant side effects of this combination therapy except for mild weight gain and moon face. This combination regimen with 5'-DFUR and MPA is considered useful as a second-line treatment for advanced breast cancer.     

Hyperfractionated irradiation with or without concurrent chemotherapy for locally advanced head and neck cancer

BACKGROUND: Radiotherapy is often the primary treatment for advanced head and neck cancer, but the rates of locoregional recurrence are high and survival is poor. We investigated whether hyperfractionated irradiation plus concurrent chemotherapy (combined treatment) is superior to hyperfractionated irradiation alone. METHODS: Patients with advanced head and neck cancer who were treated only with hyperfractionated irradiation received 125 cGy twice daily, for a total of 7500 cGy. Patients in the combined-treatment group received 125 cGy twice daily, for a total of 7000 cGy, and five days of treatment with 12 mg of cisplatin per square meter of body-surface area per day and 600 mg of fluorouracil per square meter per day during weeks 1 and 6 of irradiation. Two cycles of cisplatin and fluorouracil were given to most patients after the completion of radiotherapy. RESULTS: Of 122 patients who underwent randomization, 116 were included in the analysis. Most patients in both treatment groups had unresectable disease. The median follow-up was 41 months (range, 19 to 86). At three years the rate of overall survival was 55 percent in the combined-therapy group and 34 percent in the hyperfractionation group (P=0.07). The relapse-free survival rate was higher in the combined-treatment group (61 percent vs. 41 percent, P=0.08). The rate of locoregional control of disease at three years was 70 percent in the combined-treatment group and 44 percent in the hyperfractionation group (P=0.01). Confluent mucositis developed in 77 percent and 75 percent of the two groups, respectively. Severe complications occurred in three patients in the hyperfractionation group and five patients in the combined-treatment group. CONCLUSIONS: Combined treatment for advanced head and neck cancer is more efficacious and not more toxic than hyperfractionated irradiation alone.