s-1-(combination) and Alopecia

Here, we reported an interim analysis of feasibility and safety in the first 10 cases of 30 cases in a phase II trial of intravenous and intraperitoneal paclitaxel combined with S-1 for gemcitabine-refractory pancreatic cancer with malignant ascites.. Paclitaxel was administered intravenously at 50 mg/m2 and intraperitoneally at 20 mg/m2 on days 1 and 8 every 3 weeks, and S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7-day rest.. Between April 2011 and February 2012, ten patients were enrolled. A partial response was achieved in two patients (20%) and a disease control rate of 50%. The median time to progression and overall survival were 2.1 and 3.4 months, respectively. Malignant ascites was completely resolved in two patients (20%). Major grade 3/4 adverse events were myelosuppression including neutropenia (50%) and catheter-related infection (10%).. This novel combination chemotherapy was feasible and showed promising results in pancreatic cancer patients with malignant ascites (clinical trial registration number: UMIN000005306).

Topics: Adenocarcinoma; Aged; Alopecia; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Ascites; Catheter-Related Infections; Deoxycytidine; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Fatigue; Feasibility Studies; Female; Gastrointestinal Diseases; Gemcitabine; Hematologic Diseases; Humans; Infusions, Intravenous; Infusions, Parenteral; Male; Middle Aged; Oxonic Acid; Paclitaxel; Pancreatic Neoplasms; Prospective Studies; Salvage Therapy; Tegafur; Treatment Outcome

This Phase II study assessed the activity and safety of biweekly paclitaxel and oral S-1 as treatment for unresectable and recurrent gastric cancer. The maximum tolerated dose for this regimen had been established previously in a Phase I study performed in Japanese patients.. Chemotherapy was performed using two anticancer agents, S-1 and paclitaxel. Oral S-1 (80 mg/m(2)) was administered twice a day after meals for two consecutive weeks from Day 1 to 14, followed by a 2 week recovery period; paclitaxel (120 mg/m(2)) was administered intravenously, biweekly, on Days 1 and 15. The patient received cycles of this regimen every 4 weeks (q 28-day cycles). The primary end point was the response rate according to the Response Evaluation Criteria in Solid Tumors.. A total of 39 patients (median age, 65 years) were enrolled; 13 other patients were screened, but found to be ineligible. All patients had unresectable and recurrent gastric cancer. The most common treatment-related Grade 3/4 adverse events were neutropenia (37.5%), appetite loss, diarrhea, decreased sodium (each 5%), and anemia, increased alanine aminotransferase, general fatigue, and dizziness (each 2.5%). Almost all the patients experienced alopecia. Intent-to-treat analysis showed a response rate of 43.6%. With a median follow-up of 14 months (range 8-21 months), median survival was 256 days and the median time to progression was 4 months.. A combination regimen of biweekly paclitaxel and oral S-1 was well tolerated and showed promising activity against unresectable and recurrent gastric cancer.

Topics: Adenocarcinoma; Aged; Alopecia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Disease-Free Survival; Drug Combinations; Female; Gastrointestinal Diseases; Humans; Hyponatremia; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Analysis; Tegafur

In the present article, we report the results of phase I/II combination chemotherapy study of biweekly paclitaxel and S-1 administration in patients with advanced gastric cancer. In the phase I study, we could determine the recommended dose for the phase II study with paclitaxel and S-1 to be 120 mg/m2 and 80 mg/m2, respectively. The side effect was not so severe. The overall response was 53%. In conclusion, biweekly paclitaxel and S-1 administration can be safely combined for the treatment of advanced gastric cancer. This combined therapy represents a novel and active treatment regimen with low toxicity and can be defined as safe and effective. Now we are analyzing the result of the phase II study.

Topics: Administration, Oral; Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Infusions, Intravenous; Leukopenia; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Paclitaxel; Quality of Life; Stomach Neoplasms; Tegafur

We planned to conduct a phase II clinical study of combination therapy with CPT-11 and S-1. The antitumor effect was the primary endpoint, while the safety, progression-free survival time, and median survival time were the secondary endpoints. The subjects were untreated patients with inoperable advanced colorectal cancer aged 20-75 years. Based on the results of our previous phase I/II study in patients with gastric cancer, the dosage was established in consideration of safety for outpatient therapy. CPT-11 was administered at a dose of 100 mg/m2 (on days 1 and 15) as an intravenous infusion over 90 minutes, and oral S-1 (40 mg/m2) was administered after breakfast and dinner and then withdrawn for 2 weeks. No other serious adverse reactions occurred (either hematological or non-hematological), and all patients could receive therapy safely on an outpatient basis. Interim analysis suggested excellent results, with a response rate of 50%. Combination therapy with CPT-11 and S-1 achieved a high response rate and could be given safely. These findings suggest that the therapy has potential as first-line treatment for inoperable advanced recurrent colorectal cancer.

Topics: Administration, Oral; Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Irinotecan; Leukopenia; Middle Aged; Nausea; Neutropenia; Oxonic Acid; Remission Induction; Tegafur

We report a case in which combination chemotherapy of TS-1 and paclitaxel was effective for gastric cancer with malignant ascites, metastatic ovarian cancer and hydronephrosis. Judging from the above issue, the stage was IV and the type was Borrmann 4. The chemotherapy schedule was adjusted at the patient' s request without hindering her activities of daily living. The patient was a 53-year-old woman who suffered from gastric cancer as having malignant ascites and metastatic ovarian tumor. As an outpatient, she was treated with combination chemotherapy of TS-1 and paclitaxel for 2 cycles. The ascites had remarkably disappeared after 2 cycles. The adverse event was alopecia (grade 2), but she could continue the chemotherapy as an outpatient treatment. After completing 5 cycles of chemotherapy, we recognized the primary tumor as an endoscopic complete response.

Topics: Alopecia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Drug Administration Schedule; Drug Combinations; Female; Humans; Middle Aged; Ovarian Neoplasms; Oxonic Acid; Paclitaxel; Quality of Life; Remission Induction; Stomach Neoplasms; Tegafur

The clinical efficacy and safety of weekly paclitaxel therapy were studied retrospectively in 17 patients with advanced and recurrent gastric cancer who had previously been treated with TS-1 therapy. The overall response rate was 0%, but MST was 495 days. The adverse effects observed were grade 3 leukopenia in 2 patients (11.8%) and grade 1 and 2 alopecia in 13 patients (76.5%). However, weekly paclitaxel therapy was performed for all outpatients. Weekly paclitaxel therapy could be useful and safe as second-line chemotherapy.

Topics: Aged; Alopecia; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Quality of Life; Stomach Neoplasms; Survival Rate; Tegafur

S-1, an antineoplastic formulation of a fluorinated pyrimidine derivative containing tegafur (FT), CDHP, and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1, was recently developed by Taiho Pharmaceutical Co., Ltd., with the aim of prolonging the effective plasma concentration of 5-fluorouracil (5-FU) over that produced by FT alone and reducing its dose-limiting gastrointestinal toxicity. As a part of the S-1 toxicity study, the single-dose toxicity of S-1 as well as that of its components, CDHP and Oxo, was investigated in mice, rats, and dogs. The following results were obtained. 1. In mice and rats, excretion of diarrheal stools, salivation, and alopecia were observed after S-1 administration. In severe cases, the animals subsequently showed emaciation due to weight loss or suppressed weight gain, decreased spontaneous motor activity, an anemic appearance, bradypnea, prone position, and death. In the CDHP and Oxo treatment groups of rats, the only toxic signs were soft or diarrheal stools on the dosing day. 2. In dogs, vomiting and excretion of diarrheal, mucous, or soft stools was observed after S-1 administration. In the CDHP and Oxo treatment groups, excretion of soft and diarrheal stools and vomiting were observed relatively frequently from the dosing day until day 1. 3. In the pathological examination of the animals given S-1, mice and rats showed pulmonary congestion/edema, dark red discoloration of the mesenteric lymph nodes, atrophy of lymphatic tissues such as the thymus and lymph nodes, decreases of lymphocytes in the splenic white pulp and mesenteric lymph nodes, a decrease in bone marrow cells, congestion of the glandular stomach, and aggregates of bacteria in the lung, liver, or spleen. In dogs, abnormal changes were observed mainly in the lymphatic organs such as the thymus and lymph nodes. 4. The LD50 values of S-1 in terms of the amount FT they contained were estimated to be 549 mg/kg for mice(male), 441-551 mg/kg for rats (both sexes) and about 53 mg/kg for dogs (male). The LD50 values of CDHP and Oxo were 2000 mg/kg or higher for both rats (both sexes) and dogs (male). 5. Hematopoietic and lymphatic impairments, immunosuppression associated with respiratory were considered to be the cause of death from S-1. The toxicity of S-1 reflects the toxicity of 5-FU and was not found the different toxicity by the addition of CDHP and Oxo.

Topics: Administration, Oral; Alopecia; Animals; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Body Weight; Diarrhea; Dogs; Drug Combinations; Female; Lethal Dose 50; Lymph Nodes; Male; Mice; Motor Activity; Oxonic Acid; Pyridines; Rats; Salivation; Spleen; Survival Rate; Tegafur; Thymus Gland