Effect of CDDP/5'-DFUR combination chemotherapy for advanced or recurrent gastric cancer

CDDP/5'-DFUR combination chemotherapy was performed on 17 patients with non-resected and recurrent gastric cancer (clinical stage were IVb in all patients). They were treated with 1,400 mg/m2 of 5'-DFUR on days 1-4 orally following by withdrawal 10 days, every 2 weeks repeatedly and 80 mg/m2 of CDDP (c. i. v., on day 5, every 4 weeks). This chemotherapy was performed for at least 2 courses on all patients. Eight of 17 patients achieved a partial response and the overall response rate was 47.1% (differentiated type 57.1%, undifferentiated type 45.5%). Response rates of each lesion were as follows: primary foci 42.9%, abdominal lymph nodes 57.1%, hepatic metastasis 60.0% and ascites 33.3%, respectively. Improvement of performance status was seen in 12 of 17 patients (70.6%). The overall median survival time was 227 days. The median outpatient period was 113 days. There was no high-grade toxicity over grade 2. Therapeutic toxicity of grade 2 was manifested as renal dysfunction (23.5%), nausea/vomiting (17.6%), leukopenia (5.9%) and anemia (5.9%). We evaluated the therapeutic effect by visual examination after completion of the second course. However, poor effect and high incidence of renal dysfunction were found in patients treated with this therapy over four times. Therefore, the maximum effect seemed to be revealed after completion of the fourth course. From the present study, CDDP/5'-DFUR combination chemotherapy seems to be effective for patients with high-grade advanced gastric cancer and improved their quality of life.     

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.     

Possibilities and limits of surgical therapy of pseudomyxoma peritonei

In a retrospective study, the potential and limitations of surgical therapy of pseudomyxoma peritonei were studied in seven patients. In all patients the pseudomyxoma had originated from the appendix. All patients were primarily treated by surgery. An R0 resection at the first operation was possible in only one patient with a benign pseudomyxoma, while significant tumor debulking with improved symptoms was achieved in all other patients. If the tumor recurred relaparotomy was performed to obtain tumor reduction. The perioperative morbidity even after multiple relaparotomies was low. The survival rates ranged between 2 and 20 years with chemotherapy (5-fluorouracil) which was of particular prognostic benefit in patients with malignant pseudomyxoma peritonei. Surgical therapy is the treatment of choice in pseudomyxoma peritonei, although an R0 resection is hardly feasible. Due to the low morbidity, relaparotomy in cases of tumor recurrence always appears to be indicated. In comparison to other gastrointestinal malignancies, the survival rates in pseudomyxoma peritonei, sometimes treated with additive chemotherapy, are superior.     

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.     

Successful treatment of recurrent multiple lung metastasis from colon cancer with combination chemotherapy using methotrexate, 5-fluorouracil, and high-dose leucovorin: a case report

A 66-year-old man, who had received sigmoidectomy for sigmoid cancer in 1985, was diagnosed as having multiple lung and liver tumors in September 1988. When celiac-angiography was performed, recurrent liver metastases from sigmoid cancer were suspected and he received a transarterial embolism with ADM 30 mg and MMC 20 mg. In addition, he was treated with a sequential chemotherapy with methotrexate (MTX), 1,200 mg intravenously (6 h-infusion) followed by 5-fluorouracil (5-FU), 600 mg/m2/day and leucovorin, 300 mg/body/day in continuous infusion for 5 days from day 2 with concomitant oral administration of dipyridamole (300 mg/day) over 14 days. Treatment was repeated every 28 days for two courses. For the third course, administration of only 5-FU, leucovorin and dipyridamole was performed. As a result, the size of pulmonary lesions was prominently reduced on computed tomography. Although mucositis, anal erosion, diarrhea and thrombocytopenia were noted, no severe side effects were observed. This sequential chemotherapy appears useful for metastatic lesions from colon cancer.     

Successful treatment of orbital rhabdomyosarcoma in two infants using chemotherapy alone

In a prospective study, arthroscopic examinations were performed on 42 wrists following injury. Clinical findings, radiology, and arthrography were compared to the arthroscopic findings. Only obvious or total ligamentous ruptures found on arthroscopy were considered in the analysis. No direct correlation could be demonstrated with clinical findings or arthrography. The distribution pattern of ligament injury involving the radial and ulnar compartment of the wrist joint in 40% of the cases suggests that carpal dysfunction following injury and ligamentous tears is a more complex problem than usually accepted. The ulnar midcarpal joint seems more prone to injury than the radiocarpal portion of the wrist. This suggests an important biomechanical function of the palmar ligaments inserting on the triquetrum.     

Comparison between intraperitoneal and intravenous 5-fluorouracil administration using pancreatic cancer model of nude mouse

Carcinoma of the pancreas is a virulent malignancy. The purpose of this study was to evaluate the efficiency of 5-FU intraperitoneal administration for this malignancy. We developed a pancreatic cancer model whereby a human pancreatic cell line, MIA PaCa-2, was orthotopically transplanted to the pancreas of nude mice as cell suspension (1 x 10(6) cells). IP group (n = 6) received 5 times IP administration (4, 7, 12, 16, 20 days after implantation) of 5-FU 50 mg/kg, 1.5 ml. IV group (n = 6) received 5 times IV therapy (the same dates as IP group) of 5-FU 50 mg/kg, 0.2 ml. Control group (n = 6) received no treatment. The mice were sacrificed 42 days after implantation. The weight of the tumors of IP, IV and Control group was 0.332 +/- 0.143 g, 0.138 +/- 0.047 g and 0.329 +/- 0.085 g. Significant differences were found between IP and IV, and control. There was no difference between IP and control. This experiment demonstrated that 5 FUIP therapy for primary pancreatic cancer showed no effect and 5 FUIV therapy was much more effective.     

Combination hepatic intra-arterial 5-fluorouracil and CDDP administration with oral regimen in patients with colorectal cancer metastasis to the liver

We investigated therapeutic effectiveness and side effects of a combination weekly high-dose 5-FU plus one shot CDDP HAI (WHF + CDDP method) with oral regimen in patients with colorectal cancer metastasis to the liver. All 24 patients enrolled in this study showed 54% efficacy whereas patients combined HAI with oral regimen over one week obtained 83% efficacy for multiple liver metastasis. They showed good quality of the life during combination chemotherapy without any symptoms of metastatic lesions. The WHF + CDDP method combined with oral regimen is a promising treatment for colorectal cancer metastasis to the liver as well as extrahepatic distant organs, and this protocol may be satisfactorily accepted by most colorectal cancer laden patients because of negligible side effects.     

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.     

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.     

Current status of low-dose CDDP. 5-FU therapy for solid malignant tumors--nationwide questionnaire survey

A nation-wide questionnaire survey was undertaken concerning low-dose anticancer therapy of CDDP plus 5-FU, which involves (5-10 mg CDDP/body/day + 300-500 mg/body/day) for 4-6 weeks. Out of 1,525 cases from 130 institutions, 847 cases with evaluable lesions were collected from 79 institutions. The response rate was 56.4% in esophageal cancer, 34.3% in gastric cancer, 35.3% in colorectal cancer, 47.2% in liver cancer and 35.9% in lung cancer, respectively. Adverse effects were found to be fewer and compliance was much better than the conventional therapy. Such figures suggest that the present regimen may be more effective than any so far. Problems for medical administration such as unlicensed CDDP for colorectal cancer were pointed out, which hinder the forthcoming third phase study.     

Successful treatment of progressive multifocal leukoencephalopathy with low-dose interleukin-2

A patient with low-grade lymphoma presented 8 months after autologous marrow transplantation with dizziness, aphasia and hemiparesis. Magnetic resonance imaging (MRI) showed an abnormal T2 signal in the frontoparietal region unilaterally. Biopsy of the area demonstrated progressive multifocal leukoencephalopathy positive for JC virus and p53. Treatment with interleukin-2 at 0.5 MU/m2/day i.v. continuous infusion resulted in near complete resolution of symptoms and MRI abnormalities. The absolute number of CD3+CD4+ and CD3-CD56+ cells in the peripheral blood also increased, and the CD4/CD8 ratio normalized. She remains free of evidence of progressive multifocal leukoencephalopathy 1 year off therapy.     

Intermittent calcitriol therapy in secondary hyperparathyroidism: a comparison between oral and intraperitoneal administration

BACKGROUND: Intermittent oral or intravenous doses of calcitriol given two or three times per week are commonly used to treat secondary hyperparathyroidism (secondary HPT). This study was undertaken to compare the biochemical and skeletal responses to thrice weekly intraperitoneal (i.p.) versus oral doses of calcitriol in children with secondary HPT undergoing peritoneal dialysis (CCPD). METHODS: Forty-six patients aged 12.5+/-4.8 years on CCPD for 22+/-25 months were randomly assigned to treatment with oral (p.o.) or i.p. calcitriol for 12 months; 17 subjects given p.o. calcitriol and 16 subjects given i.p. calcitriol completed the study. Bone biopsies were performed at the beginning and at the end of the study, while determinations of serum and total ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH) and calcitriol levels were done monthly. RESULTS: Serum total and ionized calcium levels were higher in subjects treated with i.p. calcitriol, P < 0.0001, whereas serum phosphorus levels were higher in those given p.o. calcitriol, P < 0.0001. For the i.p. group, serum PTH levels decreased from pre-treatment values of 648+/-125 pg/ml to a nadir of 169+/-57 pg/ml after nine months. In contrast, serum PTH levels did not change from baseline values of 670+/-97 pg/ml in subjects given p.o. calcitriol, P < 0.0001 by multiple regression analysis. Serum alkaline phosphatase levels were also lower in patients treated with i.p. calcitriol, P < 0.0001, but there was no difference between groups in the average dose of calcitriol given thrice weekly. The skeletal lesions of secondary HPT improved in both groups, 33% of patients developed adynamic bone lesion. CONCLUSION: Differences in the bioavailability of calcitriol and/or in phosphorus metabolism may account for the divergent biochemical response to p.o. and i.p. calcitriol.     

Correlation of lethal doses of industrial chemicals between oral or intraperitoneal administration and inhalation exposure

To further explore barrier properties of the sclera, the diffusion of 3H-hydrocortisone and 14C-mannitol was measured across isolated rabbit scleral membrane. In vitro permeability studies were performed using side by side diffusion cells. Bicarbonated Ringer Solution with oxidized glutathione (GBR) at pH 7.4 was the perfusion medium, and the temperature was kept at 37 degrees C. Diffusion of hydrocortisone through the cornea was also measured to compare scleral and corneal permeation. Scleral permeability was found to be five times greater than corneal permeability. Drug analyses were performed by radionuclide counting (LSC), and permeability coefficients were obtained. In vitro metabolism of hydrocortisone was examined by incubation of tissue in hydrocortisone solution in GBR for 5 hours and 37 degrees C. Permeability coefficients of hydrocortisone diffusion through the sclera were also obtained at 25 degrees C, 15 degrees C, and 5 degrees C. Activation energy of scleral transport of hydrocortisone was calculated from an Arrhenius plot. The low activation energy suggests an aqueous pore pathway unlike permeation of the drug across the cornea which uses a transcellular pathway.     

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.     

5-FU concentrations in the blood and tumor tissue after 5'-DFUR or UFT administration in the patients with uterine cervical cancer

In order to verify the antitumor activity of fluorinated pyrimidine drugs, we conducted an investigation of the clinical pharmacology with two drugs, 5'-DFUR and UFT. Total 21 cases of cervical cancer were alloted randomly into 5'-DFUR group (daily dose 800 mg for 3 days) consisting of 11 patients and UFT group (daily dose 600 mg for 3 days) consisting of 10 patients, the unchanged substances (5'-DFUR in the 5'-DFUR group and tegafur concentrations in the UFT group) and 5-FU concentrations in serum and tissues were measured 6 hours after administration of the drugs. The 5'-DFUR concentration in the 5'-DFUR group was not detected in serum and less than a detectable limit for all of cancerous tissues, normal cervical tissues, and lymph nodes. The tegafur concentrations in the UFT treated group was 13.8 +/- 7.0 micrograms/ml for serum, 10.4 +/- 6.4 micrograms/g for cancerous tissues, 14.1 +/- 7.3 micrograms/g for normal cervical tissues, and 4.5 +/- 4.2 micrograms/g for lymph nodes. The 5-FU concentrations in the 5'-DFUR treated group were 0.018 +/- 0.046 micrograms/g for cancerous tissues, but less than a detectable limit for serum and normal cervical tissues. On the other hand, in the UFT group, 0.271 +/- 0.247 micrograms/g for a cancerous tissue, 0.035 +/- 0.018 micrograms/ml for serum, 0.125 +/- 0.073 micrograms/g for normal cervical tissues, showing significantly high values (p < 0.01, p < 0.001, and p < 0.01, respectively) compared to those in the 5'-DFUR treated group. These results suggest that UFT is a promising drug for the treatment of cancer of the uterine cervix.     

低剂量硼替佐米联合沙利度胺及化疗治疗多发性骨髓瘤35例

目的 观察低剂量硼替佐米联合沙利度胺及化疗治疗多发性骨髓瘤(MM)患者的疗效及安全性.方法 35例初治及难治复发MM患者,硼替佐米1.1 mg/m2,第0、3、7、10天,静脉注射;沙利度胺从50 mg/d开始逐渐加量至150 mg/d或患者能够耐受的最大剂量;化疗方案根据每疗程患者情况选择MP、VAD或AD方案.28 d为1个疗程,每例患者至少接受2个疗程以上治疗.达到部分缓解(PR)及以上疗效的患者应用沙利度胺150 mg/d或患者能够耐受的最大剂量维持治疗.采用2006年MM国际统一疗效标准观察疗效,根据国际癌症研究中心不良事件通用命名标准评估不良反应.结果 中位随访20个月,35例患者治疗总有效率82.8%,其中完全缓解(CR)率48.6%,良好的部分缓解(VGPR)率17.1%,PR率17.1%.3年预计无进展生存(PFS)和总生存(OS)率分别为60.92%和72.41%.达PR以上疗效患者的OS率高于未达PR患者,差异有统计学意义(P=0.004).初治及难治复发患者客观缓解率(ORR)及OS率差异无统计学意义.Ⅲ～Ⅳ度非血液学毒性主要包括乏力(3/35)、恶心、呕吐(8/35)、便秘(4/35)和周围神经病变(3/35).Ⅲ～Ⅳ度血液学毒性为粒细胞缺乏(10/35)和血小板减少(8/35).结论 低剂量硼替佐米联合沙利度胺及化疗治疗MM具有较好的疗效及安全性,沙利度胺维持治疗可延长患者PFS时间.