Soh Saitoh

Phase II study of paclitaxel with 3-h infusion in patients with advanced gastric cancer

Abstract.Abstract.Background: To increase the options for agents for gastric cancer chemotherapy, we performed a phase II clinical trial on the use of a 3-h infusion of paclitaxel to confirm its efficacy and the feasibility of its use in patients with advanced gastric cancer.Methods: Thirty-two (32) patients with measurable metastatic gastric cancer were enrolled in this study. Seventeen patients (53%) had received prior chemotherapy for metastatic disease, 4 patients (13%) had adjuvant chemotherapy alone, and 11 patients (34%) were chemotherapy-naive.Paclitaxel was intravenously infused for 3 h, at a dose of 210 mg/m2, once every 3 weeks. To prevent hypersensitivity reactions, standard premedication was administered to all patients.Results: Nine (28%; 9/32 ) objective partial responses (PRs) were observed (95% confidence interval [CI], 14%–47%), and the remaining 23 patients showed stable (12 patients; 37.5%) and progressive disease (11 patients; 34.4%). The median time to response was 20 days (range, 14–38 days). The median response duration was 87 days (range, 50–103 days). The median survival of all patients was 234 days (range, 13–646+ days). The major adverse reactions were myelosuppression (grade 3/4 leukopenia and neutropenia were observed in 59% and 88% of the patients, respectively), alopecia, and peripheral neuropathy. Peripheral neuropathy was observed in 19 patients, however, most of the patients recovered after the completion of treatment.Conclusion: A 3-h infusion of paclitaxel is an effective therapy for advanced gastric cancer and is clinically well tolerated by the patients.

Docetaxel and cisplatin in patients with advanced or recurrent gastric cancer: a multicenter phase I/II study

Abstract.Background: Because docetaxel and cisplatin are both active against gastric cancer and have different mechanisms of action, this combination may provide additive or synergistic effects against gastric cancer. This article presents a phase I study designed to determine the recommended dose of cisplatin combined with a fixed dose of docetaxel, and a subsequent phase II study that evaluated the clinical efficacy and feasibility of this combination regimen. Methods: Patients enrolled in the study had to have histologically confirmed advanced or recurrent gastric cancer with measurable disease and adequate organ function, and to be aged 20 to 75 years, with a performance status (PS) of 0 to 2. In the phase I study, docetaxel was administered at a fixed dose of 60 mg/m2 on day 1. Cisplatin was also administered on day 1, at dose levels of 60, 70, and 80 mg/m2. Where dose-limiting toxicities were not observed in more than 33.3% of patients, three patients were accrued for each dose level. Results: Recommended doses for the phase II evaluation were determined to be 60 mg/m2 of docetaxel and 80 mg/m2 of cisplatin. Although grade 3 or more severe leukopenia and neutropenia were observed in 71.4% and 82.1% of the patients, respectively, nonhematological toxicities were not severe. The overall response rate at the recommended dose level was 25.0% (7/28 patients), and the rate was 40% (6/15) for patients with liver metastases. The median survival time was 9.7 months and the 1-year survival rate was 39.3%. Conclusion: Although this study failed to demonstrate a high response rate, this regimen was feasible and might be of value in further investigations in respect to the relatively high response rate in patients with liver metastasis and the favorable survival.

Randomized controlled study of mitomycin C/carboquone/5-fluorouracil/OK-432 (MQ-F-OK) therapy and mitomycin C/5-fluorouracil/doxorubicin (FAM) therapy against advanced liver cancer.

SummaryWe have previously reported that the combination of mitomycin C, carboquone, 5-fluorouracil and OK-432, including the intra-arterial administration of mitomycin C and carboquone (MQ-F-OK therapy), was effective in the treatment of advanced liver cancer. The Cooperative Study Group conducted a controlled study on MQ-F-OK therapy and the combination of mitomycin C, 5-fluorouracil and doxorubicin, including the intra-arterial administration of mitomycin C and doxorubicin (FAM therapy), against advanced liver cancer. Forty patients with advanced primary or secondary liver cancer were enrolled in this study and randomized into the MQ-F-OK group and the FAM group. Seventeen of the 21 cases in the MQ-F-OK group and 16 of the 19 cases in the FAM group were eligible for response evaluation in accordance with the criteria of the Japan Society for Cancer Therapy. There was no significant difference in the patient characteristics between the two groups. Three cases in the MQ-F-OK group and two in the FAM group showed partial response. There was, however, no significant difference in the response rates and the prolongation of life between the two groups. As for the side-effects, only anemia was observed more frequently in the FAM group than in the MQ-F-OK group. In conclusion, we could not preferentially recommend either MQ-F-OK therapy or FAM therapy for advanced liver cancer. The performance status of the patient was one of the most important factors in the treatment of advanced liver cancer because patients with poor performance status showed poorer results.

Biweekly administration regimen of docetaxel combined with CPT-11 in patients with inoperable or recurrent gastric cancer

AbstractBackground. Both docetaxel (TXT) and irinotecan (CPT-11) are active chemotherapeutic agents for gastric cancer. We designed a biweekly administration regimen of TXT combined with CPT-11 for 4 weeks as one cycle in patients with inoperable or recurrent gastric cancer, and conducted a dose-escalation study. Methods. Patients with histologically confirmed gastric cancer were treated with the regimen. The dosage levels of TXT and CPT-11 were as follows: level 1, 30 mg/m2 and 50 mg/m2; level 2, 35 and 50 mg/m2; level 3, 40 and 50 mg/m2; level 4, 40 and 60 mg/m2; and level 5, 50 and 60 mg/m2. The dose escalation was based on the dose-limiting toxicity (DLT) observed during the first cycle. Results. Grade 4 neutropenia was observed at level 3, but no other DLT was observed at less than level 4 during the first cycle. However, three patients at level 3 could not continue treatment without a decrease in the dosage after the second cycle. Based on these results, level 2 was considered to be the clinically recommended dosages. Conclusion. Biweekly TXT and CPT-11 was well tolerated. The recommended dosages of TXT and CPT-11 for a phase II trial are 35 mg/m2 and 50 mg/m2, respectively.

Docetaxel and cisplatin in patients with advanced gastric cancer: results of Japanese phase I/II study

Two phase II monotherapy studies of docetaxel in patients with advanced gastric cancer were performed in Japan. In group A, docetaxel showed an overall response rate of 23.7% (14/59) in 59 patients, and the adverse reactions were tolerable. In group B, this agent showed the same response rate, of 23.7% (14/59) and the same adverse reaction profile.We then conducted the phase I/II studies of docetaxel and cisplatin for advanced gastric cancer. A Japanese phase I study in patients with advanced gastric cancer established that docetaxel 60 mg/m2 could be given together with cisplatin 80 mg/m2 without any dose-limiting toxicity. In a phase II trial of this combination regimen in 25 evaluable patients with advanced or recurrent disease, the overall response rate was 28% (7/25), and the response rate for liver metastases was 40% (6/15). Hematological and nonhematological toxicities were acceptable. It is concluded that this regimen is feasible and might warrant further investigation in respect to its relatively high response rate for liver metastases.

Phase II study of irinotecan (CPT-11) alone in patients (pts) with metastatic pancreatic cancer

4102 Purpose: The objective of this study was to determine the efficacy and safety of CPT-11 monotherapy in pts with metastatic pancreatic cancer. The influence of biliary drainage on the pharmacokinetics of CPT-11 was also investigated. PATIENTS AND METHODS Chemotherapy naive pts with metastatic pancreatic cancer who fulfilled the following criteria were registered: measurable metastatic disease, KPS≥50, age<75, ANC≥2000, Hgb≥10, Plts≥100K, AST&ALT≤2.5X nl, t-bili≤2.0, adequate organ function, and written informed consent. CPT-11 (100 mg/m2 as a 90-minute infusion) was administered on days 1, 8, and 15 every 4 weeks. RESULTS Forty pts were enrolled between Aug. 2001 and Nov. 2002, and 37 pts were evaluable for efficacy and safety. Their characteristics were: M/F 25/12; median age 59 years (41-74); median KPS 90 (100-70); and 2 pts with biliary drainage. Median number of courses administered was 2 (1-10). Ten pts (27%) showed a partial response (PR) using bi-dimensional criteria, while assessment using RECIST criteria indicated 8 PRs (28%) in 29 pts. Neutropenia, diarrhea, and vomiting were the common adverse events, as in other studies of CPT-11 monotherapy. The median survival time was 7.3 months. One pt was died of sepsis due to neutropenia and diarrhea induced by CPT-11. Other serious adverse events (SAE) were neutropenia and thrombocytopenia. Obstructive jaundice, elevated bilirubin and gastric variceal bleeding also occurred as drug unrelated SAE. Seven pts (including 2 with biliary drainage) were used to assess pharmacokinetics. The AUC of CPT-11 was similar between pts with or without biliary drainage, but the metabolites (SN-38, APC, and SN-38 glucuronide) showed larger AUCs in the pts with drainage. CONCLUSIONS CPT-11 monotherapy is effective for metastatic pancreatic cancer. No significant financial relationships to disclose.

Phase I-II study of biweekly paclitaxel administration with fixed-dose-rate cisplatin in advanced gastric cancer

BackgroundBoth paclitaxel (TXL) and cisplatin (CDDP) show efficacy against gastric cancer. The aim of this phase I-II study was to determine the maximum tolerated dose (MTD) and to evaluate the toxicity and efficacy of combination chemotherapy with these two agents.MethodsNineteen patients entered the phase I part of the study, and 21 patients entered the phase II part. TXL infusions were administered on days 1 and 15, with a fixed 3mg/m2 dose of CDDP.ResultsIn the phase I part of the study, we determined dose level 5, which represented a TXL dose of 18mg/m2, with CDDP 3mg/m2, to be the MTD. The recommended dose (RD) was level 4, with a TXL dose of 16mg/m2 with CDDP, 3mg/m2. In the phase II part of the study, the response rate was 25.0%; five patients had a partial response, seven had stable disease, 6 had progressive disease, and 2 were not evaluable. Grade 3 or 4 neutropenia was the most common adverse event and occurred in 65% of the patients. During treatment, 25% of the patients received granulocyte colony-stimulating factor, but febrile neutropenia was not shown in any of the patients. Major nonhematological toxicities were nausea/vomiting, anorexia, fatigue, alopecia, and sensory neuropathy. Adverse reactions of grade 3 or 4 were shown by two patients, one with anorexia (5%) and the other with sensory neuropathy (5%).ConclusionThe RD was determined to be TXL 14mg/m2, with CDDP 3mg/m2.

Antitumor effect of combination of murine recombinant interferon β, murine recombinant interferon γ and human recombinant interleukin-2 in methA-bearing mice

SummaryWe have previously reported that the combination of murine recombinant interferon β (Mu-rIFNβ) with murine recombinant interferon γ (Mu-rIFNγ) provided greater inhibition of tumor growth than did each one alone in MethA-bearing mice. In the present study the effect of addition of human recombinant interleukin-2 (Hu-rIL-2) to the combination of Mu-rIFNβ with Mu-rIFNγ on tumor growth in BALB/c mice bearing syngeneic MethA fibrosarcoma was examined. Low doses of Hu-rIL-2 (5 × 103 U or 5 × 104 U at 3-day intervals) showed no antitumor activity, while a high dose of Hu-rIL-2 (5 × 105 U) showed profound growth inhibition. The administration of IL-2 (ranging between 5 × 103 U and 5 × 105 U) in addition to the combination of IFNβ and IFNγ showed more augmented antitumor effects in a dose-dependent manner. Furthermore, the simultaneous administration of IL-2, IFNβ and IFNγ had more effective therapeutic activity, compared with the sequential administration of interferons and IL-2. These findings indicated that IL-2 in combination with IFNβ and γ was effective for cancer treatment.

The efficacy of first-line IRIS with or without bevacizumab in patients with metastatic colorectal cancer: Including multivariate analysis of two phase II studies.

603 Background: The safety and efficacy of first-line IRIS (S-1 in combination with irinotecan) and IRIS/Bev (IRIS in combination with bevacizumab [Bev]) have been evaluated in patients with metastatic colorectal cancer (mCRC). To date, no randomized studies comparing these regimens have been performed. This retrospective analysis compared efficacy data for the two regimens from separate phase II studies performed at Hokkaido Gastrointestinal Cancer Study Group (HGCSG). Methods: Patients with histologically confirmed unresectable metastatic or recurrent CRC and received no prior chemotherapy were enrolled. In the first trial, patients received irinotecan 100 mg/m2 on day 1,15 and oral S-1 40 mg/m2 twice daily on days 1-14 every 4 weeks (IRIS study: HGCSG0302). In the second trial, patients received the same regimen plus Bev 5 mg/kg on day 1,15 (IRIS/Bev study). Results: A total of 40 and 52 patients were enrolled the IRIS and IRIS/Bev studies, respectively. Patient characteristics were generally similar i...

P3-12-7STUDY OF THE MEDICAL TREATMENT OF EXTRAHEPATIC BILE DUCT CANCER AT MISAWA CITY HOSPITAL

Abstract Background: A biliary tract cancer is a disease with a bad prognosis and a high mortality rate. Although Gemcitabine, Fluopyrimidime Aniticancer Drugs, and drugs containing platinum are used as chemotherapy, radical surgery is the only method of enabling recovery. This time we studied the medical treatment of Stage I to IV of the extrahepatic bile duct cancer at our hospital. Methods: We studied the effect of various medical treatments on 40 patients of stage I to IV of the extrahepatic bile duct cancer with no medical historical verification of chemotherapy. These patients matched grade 0 to 4 accoding to the Eastern Cooperative Oncology Group with a performance status chart. The decreasing value of bilirubin, the length of the first hospitalization, and the over all survival were retroacted and examined. Results: From April, 2005 to January, 2013, 40 cases were analyzed. (a)The group of “stent only placement” had 11 patients, (b) The group of “stent placement + radiotherapy” had 7 people, (c) The group of “stent placement + radiotherapy + chemotherapy” had 12 people, (d) The group of “stent placement + chemotherapy” had 7 people, (e)The group of “operation” had 3 people. Analysis results: Bilirubin decrease values were (a) 5.8 (5.0 SD) mg/dL, (b) 12.1 (10.0 SD) mg/dL, (c) 9.9 (6.4 SD) mg/dL, (d) 9.5 (3.8 SD) mg/dL, and (e) 6.4 (4.9 SD) mg/dL, Length of first hospitalization were (a) 38.0 (27.5 SD) days, (b) 72.6 (19.9 SD) days, (c) 94.5 (34.8 SD) days, (d) 58.9 (36.5 SD) days, (e) 62.3 (8.3 SD) days. Overall survival were (a) 6.4 months, (b) 15.7 months, (c) 10.6 months, (d) 15.6 months, (e) Not less than 50%, but a judgment is statistically impossible at present. Conclusions: “Stent placement + radiotherapy” and “Stent placement + Chemotherapy” were useful for survival. However, there is a tendency for survival time to be still longer in an operation case. And it was thought important that radical surgery was possible by early detection.