A case of advanced gastric cancer with peritoneal metastasis that responded to paclitaxel plus 5-FU therapy

We report a case in which paclitaxel (PTX) plus 5-FU therapy was remarkably effective for advanced gastric cancer with peritoneal metastasis. The patient was a 41-year-old woman who had type 4 gastric cancer with peritoneal metastasis. PTX plus 5-FU therapy was performed. The regimen included 600 mg/body/day of 5-FU by continuous iv administration from day 1 to 5 and consequent administration of PTX (90 mg/body) on days 8, 15 and 22 for 28 days repetitively. After 4 courses were completed, abdominal CT revealed that ascites had disappeared and the stomach wall had become thinner. Thus,we considered the patient had a partial response, and performed total gastrectomy. After the operation, PTX plus 5-FU therapy was used for 8 courses with the same regimen. No serious adverse event was observed,and the patient maintained good QOL throughout the treatment. No sign of progressive disease was seen for 12 months after the operation. However, 18 months after beginning the treatment, peritoneal metastasis became worse, and she died 19 months after treatment had begun. Considering the effectiveness and mild toxicity, PTX plus 5-FU therapy is thought to be useful for advanced gastric cancer.     

A case of postoperative hepatic metastasis from gastric cancer responding to hepatic arterial infusion chemotherapy of paclitaxel

A 70-year-old man underwent total gastrectomy for advanced gastric cancer in January 2000. He was treated with UFT of 300 mg/day after surgery. In December 2000, liver metastasis was detected. In January 2001, treatment was switched to oral administration of TS-1 at 100 mg/day. In April 2001, there were no extrahepatic lesions. However, the metastatic liver focus showed progression of the disease (PD). TS-1 was discontinued. In May 2001, a hepatic arterial injection reservoir was inserted. Thereafter, arterial injection chemotherapy with 5-FU was administered. However, in November, liver dysfunction was exacerbated, and computed tomography (CT) revealed PD. Therefore, in December, the above chemotherapy was switched to arterial injection of paclitaxel at 100 mg, which was administered once a week for 3 weeks and discontinued for the subsequent week. In March 2002, hepatopathy had subsided at the end of the 4th course, the performance status (PS) improved and CT revealed a minor response. In June 2002, the condition deteriorated to PD. However, there were no side effects other than alopecia. During the administration period, treatment at the outpatient clinic could be safely performed. These findings suggest that hepatic arterial injection therapy with paclitaxel for liver metastasis after surgery for gastric cancer is a useful second line for 5-FU-resistant patients.     

Phase I evaluation of continuous 5-fluorouracil infusion followed by weekly paclitaxel in patients with advanced or recurrent gastric cancer

OBJECTIVE: We conducted a phase I trial of escalating doses of weekly paclitaxel (Taxol) in combination with a fixed systemic administration of 5-fluorouracil (5-FU) in patients with advanced or metastatic gastric cancer. METHODS: Patients with advanced or recurrent gastric cancer were treated with escalating doses of weekly paclitaxel as a 60 min intravenous (i.v.) infusion, along with a fixed dose of continuous 5-FU infused over 5 days. Plasma sampling was performed to characterize the pharmacokinetics and pharmacodynamics of paclitaxel. RESULTS: Eighteen patients received combination therapy at four dose levels of weekly Taxol, ranging from 60 to 90 mg/m2/week. Dose-limiting toxicities > grade 3 were observed at the 90 mg/m2/week dose level. Toxicities included anemia, neutropenia, thrombocytopenia, nausea and alopecia. Two episodes of grade 4 neutropenia occurred in two of the three patients receiving this dose. At each dose level, pharmacological studies documented the persistence of significant serum paclitaxel levels over 24 h after drug administration. The maximum tolerated dose (MTD) for this regimen was 90 mg/m2/week of paclitaxel for 3 weeks plus 600 mg/m2/day of continuous 5-FU for 5 days. CONCLUSIONS: The combination of weekly paclitaxel and 5-FU demonstrated an acceptable toxicity profile and feasible pharmacokinetic results suggesting its practical applicability. Based on these findings, the recommended dose and schedule for phase II study of combination chemotherapy is paclitaxel 80 mg/m2/week x 3 over 4 weeks, and continuous 5-FU 600 mg/m2/day x 5 days every 4 weeks.     

Effective TS-1+paclitaxel administration for gastric cancer with malignant ascites--a case report

We report a case in which TS-1 + paclitaxel (PTX) administration was effective for gastric cancer with malignant ascites. The patient was a 66-year-old male who received total gastrectomy, distal pancreatectomy and splenectomy. He complained of abdominal fullness and ascites 18 months later. The administered regimen of chemotherapy was TS-1 100 mg/day for two weeks, and PTX 120 mg/day on day 1 and 8 of TS-1 intake, followed by 1-week rest. Computed tomography (CT) showed complete loss of malignant ascites. The toxic events were grade 2 leukopenia and grade 2 alopecia.     

Combined hepatic artery 5-fluorouracil and irradiation of liver metastases. A randomized study

The effect of hepatic irradiation (RT) after intraarterial 5-fluorouracil (5-FU) was evaluated in 37 randomized patients with colorectal adenocarcinoma hepatic metastases. Patients underwent percutaneous transbrachial artery catheterization of the hepatic artery followed by 21-day continuous 5-FU infusion (CT). Hepatic irradiation of 25.5 Gy was delivered to 19 patients 14 days after completion of infusion (CT + RT). All patients received subsequent weekly maintenance 5-FU. A 37% (seven of 19) response rate was observed in CT + RT, and a 50% response rate (nine of 18) in CT: median survival was 6 months for CT + RT, and 8 months for CT, (P = 0.106). Improved survival was observed in two subsets of patients. Tumor vascularity was graded angiographically from 0 to 4+; those patients with highest vascularity (4+) had a 20-month median survival (P = 0.0009). Patients with Grade 1, well-differentiated, histologic type had a median survival of 20 months (P = 0.0001). Four patients with both 4+ vascularity and Grade 1 histologic type had 27.5 months' median survival (P = 0.0019). Age, performance status, elevated liver function tests, previous systemic therapy, and time interval between diagnosis and entry on this study did not impact on survival (P greater than 0.05), nor did these variables eliminate the significance of vascularity and grade (P less than 0.05). Survival after intraarterial 5-FU infusion was not improved by this regimen of sequential external irradiation. Regional therapy may benefit those patients with 4+ vascular tumors and/or well-differentiated tumor grade. Future trials are needed to explore the interaction of halogenated pyrimidines with irradiation and determine whether these prognostic factors can aid in patient selection for regional therapy of hepatic metastases.     

A case of inoperable scirrhous gastric cancer that responded remarkably to a combination of TS-1+paclitaxel and showed complete loss of ascites

Complete loss of malignant ascites by combination chemotherapy of TS-1+paclitaxel was experienced. The case was a 56-year-old woman who was diagnosed with inoperable scirrhous gastric cancer with malignant ascites. The administered regimen of chemotherapy was TS-1 100 mg/day (80 mg/m2) for 2 weeks. Paclitaxel 60 mg/day (50 mg/m2) on day 1 and 8 of TS-1 intake, followed by 2-weeks rest. Partial response was confirmed by gastrography and gastrofiberscope after 3 courses were performed. Furthermore, computed tomography (CT) showed complete loss of malignant ascites. Adverse reactions were grade 3 leukopenia and grade 2 nausea, vomiting and diarrhea. This result indicates the possibility of combination chemotherapy of TS-1+paclitaxel becoming an effective option in treating inoperable scirrhous gastric cancer.     

A case of hepatic metastases of sigmoid colon cancer which completely responded to systemic l-leucovorin/5-FU therapy and oral LV/UFT combination therapy

A 73-year-old man was admitted for sigmoid colon cancer with multiple hepatic metastases. The patient underwent a sigmoidectomy only, because of bronchial asthma. Then, l-leucovorin (375 mg/body) and 5-FU (750 mg/body) were injected every week. After 2 cycles (1 cycle: 6 weeks of therapy followed by a 2-week treatment break), CT scanning showed almost a complete response, without side effects such as nausea, vomiting, diarrhea and bone marrow suppression. Then, oral administration of LV and UFT was started (LV 75 mg/body/day, UFT 450 mg/body/day. After 2 weeks of therapy, there was a 1-week treatment break), and 2 years after operation this therapy was stopped because the complete response on CT scanning continued.     

An effective weekly paclitaxel administration for gastric cancer with malignant ascites--a case report

A 71 year-old woman underwent total gastrectomy for advanced gastric cancer of p stage IV (pathological findings: por1 type 3 pT3, pN3 (12p: 1/1, 16b1 int: 3/3, 16b1 lat: 2/2), P1, CY1, H0) in March 2002. She was treated with the double modulation therapy of MTX/CDDP/5-FU intraperitoneally after the surgery. After leaving the hospital, she was carrying out the chemotherapy with MTX/5-FU continually. In August 2002, she became hospitalized once again because an appetite decrease and diarrhea appeared. CT of abdomen showed that malignant ascites had obviously accumulated, and she was admitted. Because it was conceivable in all cases of an inflammation by the chemical stimulation that originated in an anticancer drug, we suspended the intraperitoneal chemotherapy. Paclitaxel 90 mg/body administration was started intravenously on a weekly basis from the end of the same month. Those symptoms improved and she was discharged from the hospital, and was continued the paclitaxel administration. In CT of the abdomen that was taken in November in 2002, malignant ascites had obviously been decreasing and disappeared completely after that.     

A case of gastric cancer with peritoneal recurrence which developed during adjuvant administration of TS-1 showing complete response by weekly docetaxel regimen

A 62-year old man had undergone total gastrectomy for Borrmann type 4 gastric cancer. No peritoneal dissemination was observed at the laparotomy. Pathological examination revealed that the tumor involved the subserosal layer, and that the lymph node metastasis extended to the left gastric nodes. Vascular and lymphatic involvement was also observed. One hundred mg/body of TS-1, an oral 5-fluorouracil (5-FU) anticancer agent, which consisted of tegafur (a prodrug of 5-FU), and two modulators (gimeracil and oteracil potassium) was given from the 16th post-operative day. A course of TS-1 consisted of consecutive administration for 4 weeks followed by 2 weeks rest. The patient complained of abdominal fullness after administration of the second course of TS-1. Computed tomography (CT) revealed massive ascites. The serum carcinoembryonic antigen (CEA) titer was elevated to 13.5 ng/ml. From these findings, the occurrence of peritoneal dissemination was suspected. Weekly docetaxel of 30 mg/m2 (40 mg/body) was given for 3 weeks followed by a week cessation. At the start of the 6th course, the serum CEA was normalized, and CT scan detected the disappearance of ascites without any new lesion. Administration of docetaxel was continued until the 10th course then stopped without relapse of the disease. No dose reduction or postponement of administration were required. The patient has survived without disease one year after cessation of the treatment. Weekly docetaxel is a safe and effective regimen for gastric cancer worth using for a second-line therapy after failure of the 5-FU-based regimen.     

A case of Stage IV gastric cancer with liver and peritoneal metastases responding completely to tailored S-1/CPT- 11 combination therapy

A 75-year-old man with advanced gastric cancer underwent distal gastrectomy with lymph node dissection(D1)and Roux-en Y reconstruction. Pathological staging was Stage IV (T3N3P1CY1M1), and curability was Cur C. He started adjuvant chemotherapy with oral administration of S-1(100 mg/body weight), but experienced grade 3 anorexia for one month. Abdominal computed tomography(CT)2 months postoperatively showed multiple liver metastases and ascites. We then conducted tailored S-1/CPT-11 as second-line chemotherapy(S-1 80 mg/body weight on days 1-5 and 8-12, CPT-11 60 mg/body weight on days 1 and 8). After 5 courses of this therapy, CT showed that the liver metastases and ascites had disappeared, leading to a complete response(CR). The only adverse event was general grade 1 fatigue. He continues to undergo oral administration of S-1(80 mg/body weight)as maintenance therapy, and maintained CR for 12 months since undergoing chemotherapy. Adverse events in tailored S-1/CPT-11 combination therapy are mild and tolerable, making this regimen a potential therapeutic strategy for patients with advanced or recurrent gastric cancer.     

A pilot study of paclitaxel and carboplatin for recurrent ovarian cancer

Combination chemotherapy with paclitaxel and platinum is the most effective regimen for advanced ovarian cancer. Second-line chemotherapy with paclitaxel (135 mg/m2, 24 h) and carboplatin (AUC 5-6) is also effective for patients who relapse on the same regimen after 6 months or more. However, it has been shown that the same efficacy and less myelosuppression can be achieved with a 3-h infusion of paclitaxel (135 mg/m2), and that dose intensification of carboplatin to an AUC values larger than 4-6 is meaningless. Therefore, we decided to conduct a pilot study of paclitaxel (135 mg/m2, 3 h) and carboplatin (AUC 4-5) for ovarian cancer patients who had relapsed or were resistant to a platinum-containing regimen without paclitaxel. Eligibility criteria included patients with relapsed or resistant ovarian cancer (no specified duration from prior therapy), age 16-75 years, with performance status 0-2, and adequate bone marrow, renal, and hepatic function. Paclitaxel was administered at a fixed dose of 135 mg/m2 followed by one of two carboplatin doses (AUC 4 or 5). Specific doses were alternated between individual patients by the order in which they entered the study. Treatment was repeated every 3 weeks, and more than 4 cycles were administered. A total of 11 patients were enrolled. Carboplatin was administered to 6 patients at an AUC of 4 and to 5 patients at an AUC of 5. The age of patients ranged from 18 to 65 years (median: 54). Other patient data (number of patients): serous (8), non serous (3), patients with measurable disease (9), assessable/CA 125 (3), study drug administration less than 6 months after prior therapy (5), study drug administration 6 months or more after prior therapy (6). Response was defined by CT and CA 125 level. CR was observed in 25% (2/8), PR in 38% (3/8), NC in 25% (2/8), and PD in 13% (1/8) of the patients. The response rate with assessable patients was 100% (3/3), and the overall response rate was 73% (8/11). Two patients with grade 1 tachycardia and grade 4 thrombocytopenia, respectively, refused further treatment after 2 cycles. No other patients experienced grade 4 hematologic toxicity or grade 3 non-hematologic toxicity. The median survival duration after paclitaxel and carboplatin therapy was 21+ months (6-26+ months). This regimen is easy to manage in heavily pretreated patients and seems to have good efficacy. To further assess the efficacy, a phase II study is needed.     

Paclitaxel, 5-fluorouracil, and leucovorin (TFL) in the treatment of metastatic breast cancer

To assess the activity of paclitaxel in combination with 5-fluorouracil (5-FU) and leucovorin in breast cancer, a phase II trial was conducted in women with metastatic disease. Toxicity, response rate, median survival, median duration of response, and median time to disease progression were measured. Between January 1994 and May 1996, 47 patients with metastatic breast cancer and an Eastern Cooperative Oncology Group (ECOG) performance status (PS) < or = 2 who had previously been treated with chemotherapy received 175 mg/m2 paclitaxel over 3 hours on day 1. After paclitaxel administration, 300 mg intravenous (i.v.) leucovorin over 30 minutes was administered followed by 350 mg/m2 i.v. push 5-FU. Both 5-FU and leucovorin were given on days 1-3. Treatment was repeated every 28 days for a minimum of 6 cycles per patient. Two (4%) patients had a complete response and 21 (45%) patients had a partial response for an overall response rate of 49% (95% confidence interval: 35%-63%). The median survival was 17.7 months, median duration of response was 8.6 months, and median time to disease progression was 6.3 months. There was no statistical difference in survival or time to progression between anthracycline-naive, anthracycline-sensitive, and anthracycline-resistant patients. Nine (19%) patients had grade 3 or 4 neutropenia, and no patient required blood or platelet transfusion. The most frequently observed nonhematologic toxicities were arthralgia and myalgia. Pharmacokinetic data were obtained on 19 patients. Responders had higher peak plasma concentrations of paclitaxel than nonresponders (4.46 vs. 2.9 micrograms/mL; P = 0.02). Paclitaxel/5-fluorouracil/leucovorin is an active, well-tolerated regimen for patients with metastatic breast cancer.     

Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solid tumour patients with poor clinical status

Melatonin (MLT) has been proven to counteract chemotherapy toxicity, by acting as an anti-oxidant agent, and to promote apoptosis of cancer cells, so enhancing chemotherapy cytotoxicity. The aim of this study was to evaluate the effects of concomitant MLT administration on toxicity and efficacy of several chemotherapeutic combinations in advanced cancer patients with poor clinical status. The study included 250 metastatic solid tumour patients (lung cancer, 104; breast cancer, 77; gastrointestinal tract neoplasms, 42; head and neck cancers, 27), who were randomized to receive MLT (20 mg/day orally every day) plus chemotherapy, or chemotherapy alone. Chemotherapy consisted of cisplatin (CDDP) plus etoposide or gemcitabine alone for lung cancer, doxorubicin alone, mitoxantrone alone or paclitaxel alone for breast cancer, 5-FU plus folinic acid for gastro-intestinal tumours and 5-FU plus CDDP for head and neck cancers. The 1-year survival rate and the objective tumour regression rate were significantly higher in patients concomitantly treated with MLT than in those who received chemotherapy (CT) alone (tumour response rate: 42/124 CT + MLT versus 19/126 CT only, P < 0.001; 1-year survival: 63/124 CT + MLT versus 29/126 CT only, P < 0.001). Moreover, the concomitant administration of MLT significantly reduced the frequency of thrombocytopenia, neurotoxicity, cardiotoxicity, stomatitis and asthenia. This study indicates that the pineal hormone MLT may enhance the efficacy of chemotherapy and reduce its toxicity, at least in advanced cancer patients of poor clinical status.     

Treatment of liver metastases with a combination of chemotherapy and hyperfractionated external radiation therapy

Twelve patients with liver metastases from colorectal cancer were treated with 5-FUdR hepatic artery, or 5-FU i.v. infusion therapy and hyperfractionated whole liver irradiation (2,100 rad in 14 fractions, two fractions/day over a period of 9 days). All 12 patients tolerated treatments well and no unusual toxicity was noted from this therapy. Response was assessed on completion of treatment and on follow-up examinations by physical examination, repeat liver function tests (LFTS), and CT scans. Symptomatic relief was achieved in all patients. Decreased liver size and improved LFTS were noted in 10/12 (83%) of patients. CT scans showed decrease in size of metastases. Survivals ranged from 16 to 120 weeks. Infusion therapy was given either by implanted infusion pump or continuous i.v. infusion therapy, 5-FUdR 0.3 mg/kg of body weight/day or 5-FU 1,000 mg/m2/day. Hyperfractionated external radiotherapy with concomitant 5-FUdR hepatic artery of 5-FU i.v. infusion therapy for liver metastases was well-tolerated, and both subjective and objective response and quality of survival were noted. Hyperfractionated external beam irradiation with concurrent chemotherapy can be effective in palliating patients with liver metastases.     

Phase I and pharmacokinetic study of 24-hour infusion 5-fluorouracil and leucovorin in patients with organ dysfunction.

BACKGROUND: Patients with hepatic or renal dysfunction are often treated with 5-fluorouracil (5-FU), but there are few data to confirm the safety of this practice. PATIENTS AND METHODS: Patients with solid tumors were eligible if they were able to fit into one of three organ dysfunction cohorts: I, creatinine >1.5 but < or =3.0 mg/dl and normal bilirubin; II, bilirubin >1.5 but <5.0 mg/dl with normal creatinine; or III, bilirubin > or =5.0 mg/dl with normal creatinine. 5-FU doses were escalated separately within each of the three cohorts. Leucovorin (LV) dosage was fixed at 500 mg/m(2). 5-FU was given as a 24-h infusion at 1000, 1800 or 2600 mg/m(2), and plasma concentrations were measured every 3 h during the first two infusions for each patient. RESULTS: Sixty-four patients were treated. Toxicities did not appear to be related to organ dysfunction cohort. A weekly dose of of 5-FU 2600 mg/m(2) produced dose-limiting toxicity (DLT) in six of 20 evaluable patients.These DLTs included grade 3 fatigue (n = 3), grade 2 neutropenia precluding weekly dosing (n = 1), grade 3 thrombocytopenia (n = 1) and grade 3 mental status changes (n = 1). There was no relationship between serum bilirubin or serum creatinine and 5-FU clearance. CONCLUSIONS: Patients with elevated bilirubin may be safely started on a weekly regimen of 5-FU 2600 mg/m(2) with leucovorin 500 mg/m(2) as a 24-h continuous infusion.     

Chemotherapy with low-dose CDDP and continuous 5-FU for the treatment of advanced gastric cancers]

INTRODUCTION: 5-fluorouracil (5-FU) has been widely used for the treatment of gastrointestinal cancers. On the basis of recent findings, low-dose Cisplatin (CDDP) and continuous venous infusion of 5-FU have shown additive or synergistic antitumor effects in experimental models. We evaluated clinical effects of low-dose CDDP and 5-FU (low-dose FP therapy) in patients with advanced gastric cancers. PATIENTS AND METHODS: In December 1993 and June 1998, 52 patients with advanced gastric cancer were entered in this study. Patients were considered eligible if they had a bidimensionally measurable tumor. 5-FU (160 mg/m2/day) was continuously infused over 24 hours using an implantable port, and CDDP (3 mg/m2/day) was infused for half an hour. The administration schedule consisted of 5-FU for 7 consecutive days and CDDP for 5 days followed by a 2-day rest every four weeks according to response and tolerance. RESULTS: Low-dose FP therapy was given 44 patients (85%). The response rate was 65.9% and median survival time was 249 days. The responder group showed good survival compared with the non-responder group. The regimen was tolerable, and the most common toxicity was anorexia (40.3%). Three patients suffered from grade 3 anorexia, leukopenia and mucositis. On the other hand, renal dysfunction occurred in 50% (two of four patients administered over 1,000 mg CDDP). These results raise the possibility that the dose-limiting factor of low-dose FP therapy may account for the total dosage of CDDP. CONCLUSION: Low-dose FP therapy promises to be effective in the clinical management of advanced gastric cancer.     

Arterial infusion therapy with low-dose cisplatin and continuous 5-fluorouracil for isolated hepatic recurrence of gastric carcinoma

Patients with metachronous liver metastasis after curative resection of gastric carcinoma generally have a poor prognosis, even when recurrence is confined to the liver. We report a patient in whom hepatic arterial infusion therapy with bolus low-dose cisplatin (CDDP) and continuous 5-fluorouracil (5-FU) was effective against large metastases confined to the liver. An 83-year-old man was admitted with huge liver metastases from gastric carcinoma. Intra-arterial bolus injection of low-dose CDDP (5 mg) and continuous intra-arterial infusion of 5-FU (250 mg/day for 7 days) was started. After four courses of this arterial infusion therapy, computed tomography scans revealed shrinkage of the liver metastases. He was followed-up as an outpatient and continued to receive the arterial infusion therapy once every 4 weeks. Throughout the course of the chemotherapy, a partial response of the liver metastases was maintained. The patient had an improved quality of life after starting the chemotherapy, and he survived for 16 months from the commencement of the therapy. Arterial infusion therapy with bolus low-dose CDDP and continuous 5-FU may be recommended for patients with isolated hepatic recurrence of gastric carcinoma. Received: September 6, 1999 / Accepted: January 31, 2000     

A long survival case of advanced colon cancer with lung metastasis and cancerous pleuritis responding to CPT-11 and S-1 combination therapy

A 71-year-old man underwent right hemicolectomy for an ascending colon cancer (stage II, Cur A) in September 2001. Adjuvant chemotherapy with tegafur/uracil was performed, but CT scans and FDG-PET, conducted in May 2003, revealed cancerous pleuritis and lung metastasis. Although 2 courses of the chemotherapy with LV+5-FU (RPMI regimen) were completed, progressive disease was confirmed. Therefore, the chemotherapy with CPT-11 (100 mg/ day; day 1, 15)+S-1 (100 mg/day; day 1-21) was started in May 2004. After completion of 6 courses, CT scan showed a partial response. Only grade 2 vomiting was noted as an adverse reaction to the treatment, however, the patient has been managed on an outpatient basis for the last 3 years with good QOL and the cancer under control. This case suggests that this combination therapy can be expected to be highly effective as a safe approach for continuously maintaining the QOL of patients with advanced or recurrent colorectal cancer.     

A trial of TS-1 administration on the basis of the pharmacokinetic study for an advanced gastric cancer patient with impaired renal function

TS-1 is an antitumor drug including 5-chloro-2,4 dihydroxypyridine (CDHP), which inhibits dihydriopyrimidine dehydrogenase (DPD) activity selectively in metabolism of 5-FU. However, TS-1 therapy tends to increase adverse events for patients with impaired renal function due to excessively high blood concentration of 5-FU, because CDHP is mainly excreted into the urine. In a 67-year-old male with advanced gastric cancer, renal dysfunction occurred during TS-1 administration as its adverse event. We studied the pharmacokinetics of 5-FU, which were analyzed on the T1/2 value and the AUC (0-infinity) of 5-FU with a single and consecutive TS-1 administration, and estimated an optimal TS-1 administration regimen for this patient. The regimen is 60 mg/body/day given in one divided dose for 28 days consecutively followed by 14 days rest. This regimen enabled a continuation of TS-1 treatment for the patient. In conclusion, individual dose adjustment using pharmacokinetic study of 5-FU might be beneficial to patients with impaired renal function.     

Weekly paclitaxel therapy effective for gastric cancer with obstructive jaundice due to peritoneal dissemination--a case report

The patient was a 61-year-old man who suffered from advanced gastric cancer, and a distal gastrectomy was performed (T3N2P1CY1, Stage IV). He was treated with chemotherapy of TS-1 alone (100 mg/day, days 1-28 with two weeks rest). Six months later he complained of lumbago and appetite loss, then was admitted to the hospital with obstructive jaundice. Total bilirubin (T-Bil) was increased to 11.3 mg/dl. CT scan examination revealed peritoneal dissemination with much ascites and dilatation of intrahepatic bile ducts. Endoscopic drainage was tried, but was discontinued due to stenosis of gastroduodenal anastomosis. Ultimately, T-Bil was elevated to 25.2 mg/dl, and he could not sleep comfortably because of a severe itch and an irritating feeling. Weekly paclitaxel therapy was started (70 mg/m(2), day 1, 8, 15, once a week for 3 weeks followed by a week rest as one cycle). One month after the first infusion therapy, the obstructive jaundice was notably improved and the ascites disappeared completely, so he was discharged. For about one year, he was treated with this chemotherapy as an outpatient. The toxic events were anemia (grade 3) and alopecia (grade 1).