Current perspectives on pyridoxine-dependent seizures

An advanced gastric cancer patient with T3N1M0 successfully underwent a curatively total gastrectomy combined with distal pancreatectomy and lymphnode dissection following ELF-P combined chemotherapy. The patient received two courses of etoposide (75 mg/m2, Day 1-5, i.v.), leucovorin (30 mg/body, Day 2-5, i.v.), 5-FU (500 mg/m2, Day 2-5, i.v.) and CDDP (60 mg/m2, Day 1, i.v.). A partial response for the primary lesion and lymphnode metastasis was obtained, and a successful curative resection of the stomach was performed. No drug adverse responses occurred. The effect of ELF-P chemotherapy was confirmed with grade 1b by histopathological examinations. Neoadjuvant chemotherapy with ELF-P may be useful as an inductive approach for advanced gastric cancer.     

Aortic dissection and Turner''s syndrome: case report and review of the literature

Combination chemotherapy with 5-FU and CDDP was given to two patients with obstructive jaundice due to intra-abdominal lymph-node metastases of advanced and recurrent gastric cancer. One patient was a primary case associated with lymph-node metastases of portal fissure and periaorta, and the other was a recurrent case associated with lymph-node metastases of hepatoduodenal ligament and periaorta. The regimen consisted of 5-FU 1,000 mg/ m2 (day 1-5, continuous infusion) and CDDP 100 mg/m2 (day 3, 1 hr drip infusion). The interval was from the 6th to 21st day. The response to chemotherapy showed shrinking of intra-abdominal lymph-nodes and reopening of the biliary tract. The patients could be discharged from the hospital without PTBD tube and enjoyed a better quality of life (QOL). This therapy is thought to be effective against obstructive jaundice due to intra-abdominal lymph-node metastases of advanced and recurrent gastric cancer.     

Combination chemotherapy of continuous infusion 5-fluorouracil and daily low-dose cisplatin in advanced gastrointestinal and lung adenocarcinoma

Continuous intravenous infusion (c.v.i.) of 5-fluorouracil (5-FU) plus daily low-dose cisplatin (CDDP) was evaluated in 45 patients with advanced and recurrent unresected colorectal, lung, gastric and pancreatic adenocarcinoma. 5-FU was given at a dose of 320 mg/m2/day, c.v.i. for 4 weeks, and CDDP between 3.5 to 7 mg/m2/day, infused for one hour five times a week for 4 weeks. Patients received 1 to 3 cycles of treatment (average 1.5 cycle). Pancreatic cancer cases needed longer treatment periods (2.25 cycles). The response rate of colorectal cancer cases was 57.7% (15/26), pancreas cancer 40%, gastric cancer 62.5%, and lung cancer 66.7%. The overall response rate was 57.8%. No severe side effects occurred in any of these cases. These data indicate that this combination 5-FU + daily low-dose CDDP chemotherapy is effective in the treatment of advanced gastrointestinal and lung adenocarcinoma.     

A case of solitary metastatic splenic tumor of ovarian carcinoma

The case was a 67-year-old female. In March, 1993, bilateral oophrectomy + total hysterectomy+omentectomy were done, for stage III ovarian cancer with peritoneal dissemination, and high CA 125 level (2100 U/ml). As postoperative chemotherapy, intraperitoneal injection of CDDP 150 mg (4 courses), and intravenous injection of CAP (CPA 500 mg/ m2 + epirubicin 25 mg/m2 + CDDP 50 mg/m2) (10 courses) were undertaken. In March, 1995, in abdominal CT scan, a solitary splenic tumor was found and the tumor marker (CA 125) was again elevated, and splenic metastasis was suspected. In June, 1995, intravenous injection of CDDP 70 mg/m2 + CPT-11 60 mg/m2 (1 course) was given, and the splenic tumor enlarged gradually. In February, 1996, a splenectomy was done. In pathological findings, the tumor proved to be poorly-differentiated adenocarcinoma the same as primary ovarian cancer, and after splenectomy, CA 125 fell below the normal value. The diagnosis was solitary splenic metastasis from ovarian carcinoma.     

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.     

Pitfalls of processed pseudogenes in RT-PCR

The patient was a 72-year-old female who had Stage IVb advanced gastric cancer with Virchow's and paraaortic lymph node metastases. She was considered nonresectable and placed on neoadjuvant chemotherapy consisting of low-dose CDDP and 5-FU. After 1 course of administration, Virchow's metastasis disappeared, and the tumor was remarkably reduced in size. However, this chemotherapy was interrupted by toxicity of grade 3 appetite loss, nausea and vomiting, so that total gastrectomy and splenectomy were performed, which were non-curative operation because of paraaortic lymph node metastases. Histopathological examination of the section of the primary tumor revealed that cancer cells had almost disappeared, and only a few atypical cells remained in the granulation tissue. Eleven months after the surgery, there has been no progression of Virchow's and paraaortic lymph node metastases. Combination chemotherapy of low-dose CDDP and 5-FU appears useful as an inductive approach to advanced gastric cancer.     

Hyperreactio luteinalis in a normal pregnancy: sonographic and MRI findings

We investigated the efficacy of combination chemo-therapy using 5-fluorouracil (5-FU), cisplatin (CDDP), and dipyridamole (DP), which is based on the concept of double biochemical modulation. Twenty-eight patients with advanced gastric cancer were treated with the simultaneous continuous intravenous (i.v.) infusion of 5-FU (800 mg/m2/day) and DP (4 mg/kg/day), and i.v. infusion of CDDP (20 mg/m2/day) for 5 days. The cycles were repeated every 4 weeks. Twelve patients (43%) had a partial response (PR), while stable disease (NC) occurred in 13 patients (46%), and progression (PD) in 3 patients (11%). An improved performance status was observed in 20 patients (71%). The carcinoembryonic antigen (CEA) level was markedly decreased in 75% of the CEA-positive patients. Toxicity was acceptable. The mean steady state plasma concentration of total DP was 6.40.5 microM, which thus seemed adequate to potentiate the cytotoxicity of 5-FU. The treatment regimen described herein thus appears to be effective, safe and well tolerated by patients with 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.     

Double mitral valve orifice. Two-dimensional and Doppler echocardiographic diagnosis

A thirty three-year-old male complaining of vomiting was diagnosed as having type 3 advanced gastric cancer of upper stomach and multiple liver metastasis, and had undergone total gastrectomy. The conclusive stage was P2H2n4se stage IVb. Intraoperatively, ethanol injection was performed for the liver metastasis under ultrasonography, and CDDP 100 mg was injected into the intra-abdominal cavity. Postoperative adjuvant therapy was added using oral fluorouracil and OK-432. Then we utilized FP chemotherapy (consisting of 5-FU and cisplatin) and radiotherapy for the bone metastasis. The patient survived 4 years and 4 months with good quality of life.     

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.     

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.     

Circadian chemotherapy in cancer patients

Continuous infusion of 5-FU at night was performed for four patients: three had liver metastasis (one with gastric cancer and two with rectal cancer) and one had local recurrence of rectal cancer. The chemotherapy schedule was 400 mg/m2/day 5-FU intraarterial or intravenous infusion from 6:00 p.m. to 6:00 a.m. for five days repeated every 3 weeks. There were one complete response, two partial responses and one with no change. It is expected that the chemotherapy of 5-FU at night will result in a high efficacy and lower toxicity.     

Induction of gene expression of antibacterial proteins by chitin oligomers in the silkworm, Bombyx mori

A 71-year-old male with advanced gastric carcinoma with paraaortic lymph node metastases underwent distal gastrectomy. Cisplatin (CDDP) 50 mg/body was administered intravenously (i.v.) on day 1 followed by the administration of 5-fluorouracil 500 mg/body/day i.v. on day 2 through day 7. After two courses of this regimen, further enlargement of paraaortic lymph nodes was revealed by CT scan, and chemotherapy was suspended. Multiple liver and lung metastases were diagnosed 6 months after initial diagnosis, and mitomycin C (MMC) 10 mg/body i.v. was administered on day 1 followed by CDDP 50 mg/body i.v. on day 2. After three courses of this regimen, partial response of the liver metastases and complete response of the lung metastases were observed, and the general condition was markedly improved without any adverse effect except slight nausea. Though the patient died of brain metastases one year after initial diagnosis, the combination chemotherapy with MMC and CDDP was nevertheless thought to improve his quality of life.     

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.     

America: where kids are getting killed

Two cases of liver metastasis from colon cancer were treated by percutaneous ethanol (PEI) and acetic acid (PAI) injection for the recurrent lesion after surgery. Case 1 was a 60-year-old female who received sigmoidectomy with partial hepatectomy, and intraarterial 5-FU infusion was done after surgery. One year later, recurrence of liver tumor was detected, and PEI and PAI were performed for the metastatic lesions of the liver. Tumor regression and histopathological examination revealed coagulative necrosis. The patient died of lung metastasis 2 years and 10 months after treatment. Case 2 was a 58-year-old-male with ascending colon cancer and liver metastasis, who received surgery, and chemotherapy with intraarterial 5-FU infusion was continued. Four months later, recurrence of liver metastasis with elevation of serum CEA was noted. The patient received PEI three times and CEA decreased. Re-operation of hepatectomy revealed complete necrosis at the site of PEI. The patient has been alive for 1 year and 6 months with a new recurrence in the liver and is receiving repeated PEI therapy. PEI and PAI seem to be useful for the treatment of unresectable liver metastasis.     

A case of multiple liver metastasis and local recurrence from rectal cancer effectively treated by arterial infusion chemotherapy using low-dose 5-fluorouracil, cisplatin and LV

The case was a 43-year-old male who complained of anal bleeding and melena. He was diagnosed as rectal cancer with multiple liver metastases. Mile's operation with hepatic arterial cannulation was performed. This patient received 10 courses of arterial infusion chemotherapy using low-dose 5-FU, CDDP and LV. Tumor size of liver lesions significantly decreased. Internal iliac arterial cannulation was also performed for local recurrence. He received 3 courses of arterial infusion chemotherapy using the same regimen. The size of local recurrence also decreased. He had no side effect except mild epigastralgia and dermatitis around the stoma with good QOL.     

Bone mass in middle-aged osteoporotic men and their relatives: familial effect

Combination chemotherapy with continuous infusion 5-FU, 350 mg/m2/day and low-dose CDDP between 5 to 10 mg/body/day (day 1-5) was evaluated in 46 patients with unresectable gastric (34), colorectal (10) and biliary tract (2) carcinoma. This regimen was repeated for 4 weeks. The overall response rate was 45.7% (21/46), but the resectable rate was only 10.9% (5/46). Toxic response (> grade 2) was 22% (10/46). After chemotherapy, the patients preserved good performance status and quality of life. Median survival time was about 11 months, and there was no significant difference between CR or PR cases and NC one. Survival time of patients correlated not to the reduction rate of tumor but to conditions of hosts (e.g., performance status, quality of life). These results suggested that this therapy is an effective palliative chemotherapy for patients with unresectable gastrointestinal carcinoma.     

Two cases of relapse or refractory germ cell tumor who had been treated with combination chemotherapy of cisplatin and carboplatin

We tried a combination chemotherapy with cisplatin (CDDP) and carboplatin (CBDCA) (CDDP/CBDCA regimen) as salvage therapy for 2 cases with recurrent or refractory Germ Cell Tumor (GCT). Case 1 was a 29-year-old man with 2nd relapsed embryonal carcinoma and seminoma originating from testis. Case 2 was a 23-year-old man with primary refractory embryonal carcinoma and yolk sac tumor originating from mediastinum. CDDP and CBDCA were administered at the dose of 120 mg/m2 and 350 mg/m2 on day 1, and vinblastin was administered at the dose of 10 mg/body on day 2. In one of two cases, a complete response was obtained. Non-hematologic toxicity of CDDP/CBDCA regimen was tolerable. It is suggested that this combination chemotherapy is useful for GCT recurrence.     

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.     

A case report: multiple liver metastasis of gastric cancer responding to intraarterial infusion of MTX and 5-FU

In a 63-year-old male patient with gastric cancer having multiple liver metastases, the metastatic lesions responded well to postoperative staggered intraarterial infusion therapy with MTX and 5-FU. The intraarterial infusion therapy was administered once a week. A total of 5 courses of this therapy produced marked regression of liver metastases and remarkable necrosis. The effect was thus rated as PR. The patient is healthy and has been successfully rehabilitated. His dose is oral 5-FU (200 mg x 2).