Chong Kun Im

Association of the ABCB1 gene polymorphisms 2677G>T/A and 3435C>T with clinical outcomes of paclitaxel monotherapy in metastatic breast cancer patients

BACKGROUND ABCB1 is responsible for multidrug resistance, the principal mechanism by which many cancers develop resistance to chemotherapeutic drugs. There is a controversy whether ABCB1 gene polymorphisms correlate with survival and response in cancer patients treated with chemotherapy. We evaluated the association between clinical outcome (safety and efficacy) of paclitaxel monotherapy in metastatic breast cancer patients with ABCB1 gene polymorphisms 2677G>T/A or 3435C>T. PATIENTS AND METHODS Patients with metastatic breast cancer were treated with 175 mg/m(2) paclitaxel per 3-week cycle. Peripheral blood mononuclear cells from patients were used to genotype ABCB1 2677G>T/A and 3435C>T polymorphisms. Genotypes were investigated for their association with tumor response, survival, toxicity, and chemoresistance. RESULTS ABCB1 3435 CT showed a significantly lower disease control rate than the CC genotype (P = 0.025). ABCB1 3435 CT was correlated with shorter overall survival (OS) in Cox regression analysis (P = 0.026). The 2677 GG genotype showed a significant association with chemoresistance to paclitaxel and anthracycline (P = 0.04 and 0.04, respectively). None of the ABCB1 genotypes correlated with toxicity. CONCLUSIONS ABCB1 genotypes may be a predictor of paclitaxel activity as well as a prognostic factor in metastatic breast cancer patients.

A randomized phase 2 study of docetaxel and S-1 versus docetaxel and cisplatin in advanced gastric cancer with an evaluation of SPARC expression for personalized therapy

The purpose of this study was to compare 2 weekly docetaxel‐based regimens as first‐line treatments for advanced gastric cancer and to investigate the expression of secreted protein acidic and rich in cysteine (SPARC) and its abilities to predict treatment‐related clinical outcomes.

Phase II study of combination chemotherapy of 5-fluorouracil, low-dose leucovorin, and oxaliplatin (FLOX regimen) in pretreated advanced gastric cancer

BACKGROUND This phase II study describes the efficacy and safety of combination chemotherapy of 5-fluorouracil (5-FU), low-dose leucovorin, and oxaliplatin (FLOX regimen) for pretreated advanced gastric cancer. PATIENTS AND METHODS Patients who had been previously treated with greater than or equal to one regimen were enrolled. Patients received an oxaliplatin 75 mg/m(2) on day 1, 5-FU 1000 mg/m(2) on days 1-3, and leucovorin 20 mg/m(2) on days 1-3, every 3 weeks. The primary end point was overall survival (OS). RESULTS Among the 52 patients enrolled, 26 patients were treated as second line, and the remaining 26 patients were enrolled as third- or fourth line. A total of 203 cycles of chemotherapy were administered with the median being three cycles (range 1-15) per patient. The median OS was 6.6 months [95% confidence interval (CI) 4.5-8.8] and the median progression-free survival was 2.5 months (95% CI 1.9-3.0). The response rate was 4% (95% CI 0-9%), and the disease control rate was 48% (95% CI 34-62%). The most common toxic effects of grade 3/4 were neutropenia (16%) and vomiting (6%). CONCLUSIONS The FLOX regimen showed modest activity as a salvage treatment in pretreated advanced gastric cancer with a favorable compliance.

Docetaxel versus paclitaxel combined with 5-FU and leucovorin in advanced gastric cancer: combined analysis of two phase II trials.

PURPOSE This is an ad hoc analysis of two phase II studies which compared the efficacy and safety of two taxanes (paclitaxel and docetaxel) combined with 5-fluorouracil (5-FU) and leucovorin (LV) in advanced gastric cancer. MATERIALS AND METHODS Patients with advanced gastric adenocarcinoma who were untreated or had only received first-line chemotherapy, were treated with either paclitaxel (PFL; 175 mg/m(2)) or docetaxel (DFL; 75 mg/m(2)) on day 1, followed by a bolus of LV (20 mg/m(2) days 1~3) and a 24-hour infusion of 5-FU (1,000 mg/m(2) days 1~3) every 3 weeks. The primary endpoint was overall response rate (ORR) and the secondary endpoint included survival and toxicity. RESULTS Sixty-six patients received DFL (first-line [n=38]; and second-line [n=28]) and 60 patients received PFL (first-line [n=37]; and second-line [n=23]). The ORRs were not significantly different between the 2 groups (DFL, 26%; PFL, 38%). With a median follow-up of 9.5 months, the progression free survival was 5.2 months (95% confidence interval [CI], 4.2~6.5 months) for DFL and 3.3 months (95% CI, 1.3~5.5 months) for PFL (p=0.17). The overall survival was also comparable between the patients who received DFL and PFL (10.0 months [95% CI, 7.2~12.5 months] and 13.9 months [95% CI, 10.9~19.2 months], respectively; p=0.37). The most frequent grade 3~4 adverse event was neutropenia (DFL, 71%; PFL, 62%). DFL and PFL had different non-hematologic toxicities; specifically, grade >or=3 mucositis (5%) and diarrhea (3%) were common in DFL, while nausea/vomiting (15%) and peripheral neuropathy (5%) were common in PFL. CONCLUSION Thus, the two taxanes had similar efficacy in the treatment of advanced gastric cancer, but different toxicity profiles. Prospective comparative studies are required to further clarify the role of taxanes in the treatment of advanced gastric cancer.

A Phase II Feasibility Study of Weekly Paclitaxel in Heavily Pretreated Advanced Gastric Cancer Patients with Poor Performance Status

Purpose: We investigated the efficacy and safety of weekly paclitaxel monotherapy in previously treated patients with advanced gastric cancer (AGC) and poor performance status (PS) according to the Eastern Cooperative Oncology Group (ECOG). Patients and Methods: Patients with evaluable disease who failed at least one previous chemotherapy and had a PS of 2–3, received paclitaxel 70 mg/m2 on days 1, 8 and 15 every 4 weeks. Results: The median overall survival (OS) was 5.5 months (95% confidence interval, CI, 3.3–7.8) and progression-free survival was 2.1 months (95% CI, 1.2–3.0). The overall response rate was 3.8% and the disease control rate was 25.0%. Treatment-related toxicities were tolerable. OS was 7.1 (95% CI, 5.4–9.5) and 3.7 months (95% CI, 2.1–5.3) for patients with PS-ECOG 2 and 3, respectively (p < 0.001). When evaluated according to the previous treatment, OS was 5.1 (95% CI, 3.3–7.0) and 6.5 months (95% CI, 3.8–9.3) for patients receiving two and three or more lines of treatment, respectively (p = 0.815). With multivariate analysis, PS was a significant factor for OS. Conclusion: Survival in patients treated with weekly paclitaxel monotherapy was comparable to other second- or third-line chemotherapies for AGC, with acceptable toxicities in previously treated patients with poor PS.

A phase II study of a combined biweekly irinotecan and monthly cisplatin treatment for metastatic or recurrent gastric cancer.

Background:There is no universally confirmed standard chemotherapeutic regimen for advanced gastric cancer (AGC). The aim of this study was to investigate the efficacy and safety of combined biweekly irinotecan and monthly cisplatin treatments of patients with AGC. The primary end point was progression-free survival. Material and Methods:AGC patients with or without measurable lesions received 70 mg/m2 irinotecan on days 1 and 15, and 80 mg/m2 cisplatin on day 1 every 4 weeks. Results:Of 40 enrolled patients, 21 patients had measurable disease. With a median follow-up duration of 35 weeks, the median progression-free survival and overall survival were 2.2 months and 8.0 months, respectively. The progression-free survival rate at 6 months was 30.0%. The most common adverse event of grade 3 to 4 was neutropenia (32.5%). Grade 3 diarrhea was observed in 2 patients (5.0%). There was no treatment-related death. Conclusion:Current combined biweekly irinotecan and monthly cisplatin treatment did not show activity comparable with other active regimens in AGC.

Comparison of taxane-based (docetaxel or paclitaxel) regimens combined with 5-fluorouracil continuous infusion and low dose leucovorin for advanced gastric carcinoma: Analysis of two phase II trials

15679 Background: We analyzed two phase II studies of paclitaxel- or docetaxel-based regimens combined with the same dose and schedule of 5-fluorouracil (5-FU) and leucovorin (LV) in advanced gastric cancer. Methods: Patients with advanced gastric adenocarcinoma, a performance status ≤ 2, and adequate organ functions received paclitaxel 175 mg/m2 (FLTaxol) or docetaxel 75 mg/m2 (FLTaxotere) on day 1 followed by a leucovorin bolus 20 mg/m2 (day 1–3) and a 24-hour infusion of 5-FU 1,000 mg/m2 (day 1–3) every 3 weeks. Prophylactic granulocyte colony-stimulating factor (G-CSF) was administered for FLTaxotere from day 4 to 8. On the other hand G-CSF was administered therapeutically for FLTaxol when absolute neutrophil count was ≤ 500/μL. Treatments were continued until disease progression, unacceptable toxicity, or patients withdrawal. Results: 60 patients were enrolled in FLTaxol study (37 first-line + 23 second-line) and 66 patients were enrolled in FLTaxotere study (38 first-line + 28 second-line). Overall...