Boram Han

Phase II trial of gemcitabine and S-1 for patients with advanced pancreatic cancer.

AbstractPurposenTo evaluate the efficacy and safety of combined gemcitabine and S-1 as first-line chemotherapy for patients with locally advanced or metastatic pancreatic cancer.MethodsThis study included patients who had been diagnosed with unresectable, locally advanced or metastatic adenocarcinoma arising from the pancreas, which was histologically or cytologically confirmed and involved at least 1 unidimensionally measurable lesion. The regimen consisted of intravenous 1,000xa0mg/m2 gemcitabine on day 1 and 8 combined with oral S-1 on days 1–14 every 21xa0days. The dosage of S-1 was based on the body surface area (BSA) as follows: 40xa0mg bid (total 80xa0mg/day) for a BSA ofxa0<1.25, 50xa0mg bid (total 100xa0mg/day) for a BSA ofxa0≥1.25 butxa0<1.5, and 60xa0mg bid (total 120xa0mg/day) for a BSA ofxa0≥1.5. Treatment consisted of at least 2 courses unless rapid disease progression was noted. The primary end points were the response and disease control rates, and the secondary end points were toxicity and survival.ResultsThirty-seven patients were enrolled between August 2005 and December 2010. The median number of chemotherapy cycles was 4 (range 1–28 cycles). Response to treatment could be evaluated in 31 patients. None of the patients showed complete response, but 5 achieved partial response. The response rate was thus 13.5xa0% [95xa0% confidence interval (CI) 2.7–24.3xa0%] in the intent-to-treat population. Sixteen patients (43.2xa0%; 95xa0% CI 27–59.5xa0%) showed stable disease, and the overall disease control rate was 56.8xa0% (95xa0% CI 40.6–72.9xa0%). For all 37 patients, the median progression-free survival was 4.6xa0months (95xa0% CI 1.8–7.6xa0month), and the median overall survival was 9.4xa0month (95xa0% CI 5.8–12.6xa0month). Chemotherapy-related grade 3/4 hematological toxicities were neutropenia (36.1xa0%), leucopenia (22.2xa0%), and anemia (13.9xa0%). The non-hematological toxicities were generally mild.ConclusionsCombination chemotherapy with gemcitabine and S-1 was effective, convenient, and safe in patients with advanced pancreatic cancer.

Phase II study of gemcitabine and S-1 combination chemotherapy in patients with metastatic biliary tract cancer

PurposeA phase II study was conducted to evaluate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with metastatic biliary tract cancer (BTC).MethodsPatients with pathologically confirmed, unresectable, recurrent, or metastatic adenocarcinoma that originated from the intrahepatic or extrahepatic biliary ducts or gallbladder were assessed for eligibility. The primary end point was the overall response rate (ORR). The treatment consisted of 1,000xa0mg/m2 intravenous gemcitabine administered over 30xa0min on days 1 and 8, and 80xa0mg/m2 oral S-1 on days 1–14 of each cycle. The treatment was repeated every 3xa0weeks.ResultsThirty-eight patients were enrolled between November 2005 and 2010. All patients had metastatic disease, and the primary sites of cancer were as follows: gallbladder in 12 (31.6xa0%), intrahepatic and extrahepatic bile ducts in 23 (60.5xa0%), and the ampulla of Vater in 3 (7.9xa0%) patients. One patient achieved a complete response, and six experienced a partial response. The ORR was 20.6xa0% (95xa0% CI 8.5–36.7] in the per-protocol (PP) population, and 18.4xa0% (95xa0%CI 6.1–30.7) in the intention-to-treat (ITT) population; the median response duration was 10.8xa0months. Nineteen patients had stable disease, and the disease control rate was 76.5xa0% (95xa0%CI 60.6–87.6) in the PP population. The median progression-free survival was 4.4xa0months (95xa0%CI 1.8–6.9), and the median overall survival was 9.0xa0months (95xa0%CI 4.0–13.9) with a 1-year survival rate of 44.7xa0% (95xa0%CI 29.0–61.5) in the ITT population. Grade 3/4 hematologic toxicities, neutropenia, anemia, and thrombocytopenia were observed in 13 (37.1xa0%), 9 (25.7xa0%), 2 (5.7xa0%), and 2 (5.7xa0%) patients, respectively. One patient experienced a grade 3 febrile neutropenia without any documented infection. The grade 3/4 non-hematologic toxicities were hepatic toxicity (11.4xa0%), anorexia (2.9xa0%), and renal toxicity (2.9xa0%).ConclusionGemcitabine and S-1 combination chemotherapy showed acceptable efficacy and favorable toxicity profiles. Therefore, it might offer an alternative therapeutic strategy in patients with BTC.

Phase II study of docetaxel, oxaliplatin, and S-1 therapy in patients with metastatic gastric cancer

BackgroundAlthough the docetaxel, 5-fluorouracil, and cisplatin triplet has yielded significant improvements in time to progression, overall survival, and overall response rate, the high incidence of severe adverse events limits the use of the docetaxel, 5-fluorouracil, and cisplatin triplet. To overcome this limitation, we evaluated the efficacy and safety of the combination of docetaxel, oxaliplatin, and S-1 for the treatment of metastatic gastric cancer.MethodsChemotherapy-naive patients with pathologically proven unresectable recurrent or metastatic gastric adenocarcinoma were assessed for eligibility. Docetaxel at 52.5xa0mg/m2 and oxaliplatin at 105xa0mg/m2 were administered intravenously on day 1, and S-1 was administered orally at 80xa0mg/m2 on days 1–14 of every 21-day cycle.ResultsForty-four patients (median age 54.5xa0years) were enrolled. All patients had metastatic disease. A total of 340 cycles of chemotherapy were administered (median of eight cycles per patient; range 1–36 cycles). Toxicities were evaluated in 43 patients, and the responses were evaluated in 40 patients. Major toxicities included grade 3/4 neutropenia (37.2xa0%) and leukopenia (27.9xa0%). The overall response rate was 54.5xa0% [95xa0% confidence interval (CI) 40.1–68.3xa0%] in the intention-to-treat population. The median progression-free survival and overall survival were 7.6xa0months (95xa0% CI 6.2–9.0xa0months) and 12.0xa0months (95xa0% CI 6.9–17.2xa0months), respectively.ConclusionThese data suggest that the docetaxel, oxaliplatin, and S-1 combination regimen is effective and relatively well tolerable, and it seems to have potential to be a reasonable therapeutic strategy in patients with metastatic or recurrent gastric cancer.

A Phase II Study to Evaluate the Efficacy of Ramosetron, Aprepitant, and Dexamethasone in Preventing Cisplatin-Induced Nausea and Vomiting in Chemotherapy-Naive Cancer Patients

Purpose Combination therapy with aprepitant, serotonin receptor antagonist, and steroids improves the complete response rate of both acute and delayed chemotherapy-induced nausea and vomiting (CINV). However, it is not known whether ramosetron is suitable for administration in combination with aprepitant. Therefore, we conducted a multicenter, open-label, prospective, phase II study in order to assess the efficacy and tolerability of combination therapy with ramosetron, aprepitant, and dexamethasone (RAD) for prevention of cisplatin-based CINV in chemotherapy-naïve patients with solid cancers. Materials and Methods Forty-one patients with various solid cancers (31 male and 10 female; median age, 59 years) who received treatment with highly emetogenic chemotherapy (median cisplatin dose, 70 mg/m2; range 50 to 75 mg/m2) were enrolled in this study. Oral aprepitant (125 mg on day 1; 80 mg on days 2 and 3), intravenous ramosetron (0.6 mg on day 1), and oral dexamethasone (12 mg on day 1; 8 mg on days 2-4) were administered for prevention of CINV. Results The complete response (no emesisand retching and no rescue medication) rate was 94.9% in the acute period (24 hours post-chemotherapy), 92.3% in the delayed period (24-120 hours post-chemotherapy), and 92.3% in the overall period (0-120 hours). The absolute complete response (complete response plus no nausea) rate was 74.4% in the acute period, 51.3% in the delayed period, and 46.2% in the overall period. There were no grade 3 or 4 toxicities related to these antiemetic combinations. Conclusion RAD regimen is a safe and effective antiemetic treatment for prevention of CINV in patients receiving highly emetogenic chemotherapy.

Second-Line Irinotecan, Leucovorin, and 5-Fluorouracil for Gastric Cancer Patients after Failed Docetaxel and S-1.

Background. This retrospective study aimed to assess the efficacy and toxicities of second-line chemotherapy with irinotecan, leucovorin, and 5-fluorouracil (5-FU) in metastatic gastric cancer (MGC) patients previously treated with docetaxel and S-1 with or without oxaliplatin (DS/DOS). Patients and Methods. We reviewed the data of patients who had previously been treated with first-line DS/DOS and received biweekly irinotecan-based chemotherapy (FOLFIRI/IFL) between October 2004 and November 2011. Results. A total of 209 cycles were administered to 35 patients, with a median of 4 (range, 1–22) cycles each. The overall response rate in 29 response-assessable patients was 17.2%, including 2 complete and 3 partial responses. The median progression-free and overall survivals were 3.81 (95% confidence interval [CI], 1.82–5.80) months and 6.24 (95% CI, 1.44–11.04) months, respectively. The major grade 3/4 toxicity was neutropenia (8.6%). Conclusion. FOLFIRI/IFL chemotherapy showed modest antitumour activity and tolerable toxicities in DS/DOS-treated MGC patients.

A dose-finding study for oxaliplatin, irinotecan, and S-1 (OIS) in patients with metastatic or recurrent gastrointestinal cancer

PurposesTo determine the maximum tolerated dose (MTD), recommended dose (RD), and activity of combined oxaliplatin, irinotecan, and S-1 chemotherapy for metastatic or recurrent gastrointestinal (GI) cancer.MethodsOxaliplatin and irinotecan were administered intravenously on day 1, and S-1 was administered orally on days 1–7, every 2xa0weeks. This phase I study used the following dose levels for oxaliplatin/irinotecan/S-1: level 1, 85/120/60xa0mg/m2; level 2, 85/120/80xa0mg/m2; level 3, 85/120/100xa0mg/m2; level 4, 85/150/100xa0mg/m2; and level 5, 85/180/100xa0mg/m2. Treatment was repeated for a maximum of 12 cycles, until disease progression, or until unacceptable toxicity.ResultsTwenty-four patients were enrolled between October 2012 and February 2014 (median age 59xa0years). During the first cycle, one of the six patients in levels 1, 3, and 4 developed a dose-limiting toxicity (grade 3 febrile neutropenia), and none of the three patients in level 5 developed a dose-limiting toxicity. As the planned maximum dose did not reach the MTD, the level 5 dose was defined as the RD. Twenty-one patients were evaluated for response, which included 2 cases of complete response and 8 cases of partial response, with an overall response rate of 47.6xa0%.ConclusionsThe combination of oxaliplatin, irinotecan, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced GI cancer. The RD was 85xa0mg/m2 of oxaliplatin, 180xa0mg/m2 of irinotecan, and 100xa0mg/m2 of S-1 every 2xa0weeks.

A phase II study of capecitabine and oral leucovorin as a third-line chemotherapy in patients with metastatic colorectal cancer

AbstractPurposenThis study was conducted to evaluate the efficacy and safety of the combination of capecitabine and oral leucovorin (LV) as a third-line chemotherapy for patients with metastatic colorectal cancer (CRC) showing resistance to irinotecan- and oxaliplatin-containing regimens.MethodPatients who showed disease progression while receiving or within 6xa0months of discontinuing irinotecan- and oxaliplatin-containing regimens received capecitabine 825xa0mg/m2 in combination with oral LV at a fixed dose of 30xa0mg, twice a day for 2xa0weeks followed by a 1-week rest.ResultsTwenty-five patients were enrolled from July 2011 to June 2014. Three patients achieved PR, and 11 showed SD. The overall response rate was 12xa0%, and disease control rate was 56xa0%. With a median follow-up of 6.8xa0months, the median time to progression was 2.8xa0months and the median overall survival was 7.1xa0months. The most common non-hematologic toxicity was hand-foot syndrome (40xa0%), followed by mucositis (28xa0%) and diarrhea (12xa0%). Grade 3 hand-foot syndrome occurred in two patients (8xa0%), and grade 3 mucositis in one. Hematologic toxicities were mild, and only one patient developed grade 3 thrombocytopenia.ConclusionThe combination of capecitabine and oral LV showed a modest activity and tolerable toxicity profile in metastatic CRC patients pretreated with irinotecan- and oxaliplatin-containing regimens. Oral LV seems to be able to reduce the usual dose of capecitabine when the two drugs are combined.

Phase II study of oxaliplatin, irinotecan and S-1 therapy in patients with advanced gastric cancer: the Korean Cancer Study Group ST14-11

BackgroundDoublet chemotherapy of platinum and 5-fluorouracil is a standard first-line treatment for patients with unresectable gastric cancer. Although the addition of taxane or irinotecan to this regimen has yielded promising efficacy, its use has been limited due to severe toxicities. To overcome this limitation, we evaluated the efficacy and safety of the combination of irinotecan, oxaliplatin, and S-1 (OIS) for the treatment of advanced gastric cancer.MethodsChemotherapy-naïve patients with pathologically proven advanced gastric adenocarcinoma were assessed for eligibility. Irinotecan (135xa0mg/m2) and oxaliplatin (65xa0mg/m2) were administered intravenously on day 1, and S-1 (80xa0mg/m2/day) was administered orally on days 1–7 of every 2-week cycle.ResultsForty-four patients (median age 57xa0years) were enrolled and all but one patient had a good performance status (ECOG 0 or 1). A total of 529 cycles were administered, with a median of 9.5 (range 1–31) cycles per patient. The overall response rate was 61.4% (95% confidence interval [CI] 46.6–74.3). The median progression-free survival and overall survival were 10.8xa0months (95% CI 7.6–14.0) and 15.4xa0months (95% CI 12.6–18.2), respectively. Major toxicities included grade 3/4 neutropenia (38.6%), febrile neutropenia (13.6%), abdominal pain (9.1%), and diarrhea (9.1%).ConclusionThese data suggest that the OIS regimen is effective and relatively well tolerated in patients with advanced gastric cancer. Given that all the patients treated, but one, had a good performance status, these results must be confirmed in a patient population more representative of regular clinical practice.Trial RegistrationClinicalTrials.gov Identifier: NCT02527785.

A Muti-center, Randomized Phase II Study of Oxaliplatin and S-1 versus Capecitabine and Oxaliplatin in Patients with Metastatic Colorectal Cancer

Background: Capecitabine plus oxaliplatin (XELOX) is considered one of the primary chemotherapy regimens for patients with metastatic colorectal cancer (CRC). Oxaliplatin plus S-1 (OS) has also demonstrated significant efficacy in CRC. We performed this randomized phase II study to evaluate the efficacy and toxicity of XELOX versus OS as first-line chemotherapy in patients with metastatic CRC. Methods: Patients were assigned randomly to receive either OS or XELOX chemotherapy. Oxaliplatin was administered intravenously to all patients at a dose of 130 mg/m2 on day 1. Patients received either S-1 (40 mg/m2) or capecitabine (1,000 mg/m2), twice a day for 2 weeks, followed by a 1-week rest. Results: Forty-two patients were assigned to the OS arm and 44 to the XELOX arm. The overall response rate was 33.3% (95% CI, 18.8-47.2) in the OS arm and 40.9% (95% CI, 25.5-54.4) in the XELOX arm (P = 0.230). The disease control rate was significantly higher in the OS arm than the XELOX arm [92.9% (95% CI, 83.7-100) versus 77.3% (95% CI, 64.5-89.4), P = 0.044]. With a median follow up of 17.9 months, the median progression-free survival was 6.1 months in the OS arm and 7.4 months in the XELOX arm, respectively (P = 0. 599). The median survival time was 18.7 months in the OS arm and 20.1 months in the XELOX arm (P = 0.340). The most common grade 3/4 hematologic toxicity was thrombocytopenia in both arms (19.0% for OS and 28.6% for XELOX). Grade 3/4 neutropenia was observed more frequently in the XELOX arm than the OS arm (16.7% vs. 2.4%, P = 0.026). Conclusion: Both OS and XELOX were effective and well tolerated in patients with metastatic CRC. Our results indicate that the combination of oxaliplatin and S-1 is a possible additional therapeutic strategy for such patients.

The positive effects of one-hour intravenous administration of bortezomib on peripheral neuropathy in multiple myeloma patients.

Bortezomib-induced peripheral neuropathy (BiPN) in multiple myeloma (MM) patients is a common and serious side effect. Currently, it has been reported that subcutaneous (SC) administration of bortezomib decreases the incidence of BiPN as compared to standard intravenous (IV) bolus injection without any differences in efficacy. However, there are reports of severe injection site reaction following SC administration of bortezomib. The aim of this study was to evaluate the response rate and incidence of BiPN following one-hour IV infusion of bortezomib. The data was retrospectively collected from MM patients who had been treated with IV administration of bortezomib for one hour. Twenty-three patients were evaluated (median age 72 years, 13 males). The median number of treatment cycles was 5 (range 2–10). The cumulative bortezomib dose was 26.0u2009mg/m2 (14.3–66.3) and percent of actual per expected cumulative dose was 90% (50–100). The overall response (complete response plus partial response) rate was 65%. The incidence of BiPN was 57% (n = 13) and incidence of severe neuropathy was 4% (n = 1). One-hour IV infusion of bortezomib was an effective regimen for MM with reduced incidence of severe BiPN. This route of administration of bortezomib could be an alternative mode of delivery for patients with severe injection site reactions following SC administration.