Dae Ro Choi

A phase II study of pemetrexed and carboplatin as a salvage therapy for platinum-pretreated patients with non-small cell lung cancer

BACKGROUNDnAlthough platinum-based doublet chemotherapy is considered as standard of care for patients with advanced non-small cell lung cancer (NSCLC), most of them are eventually supposed to experience disease progression. Pemetrexed, docetaxel, erlotinib, and gefitinib have been shown to be active as monotherapy for pretreated patients. In this study, the efficacy of pemetrexed and carboplatin as a salvage therapy for patients with advanced NSCLC is evaluated.nnnPATIENTS AND METHODSnFrom March 2007 to February 2009, 32 patients who were diagnosed with inoperable NSCLC and treated with one or more prior cisplatin-based chemotherapies were enrolled. Treatment consisted of pemetrexed 500 mg/m(2) over a 10-min intravenous infusion and carboplatin at an AUC 5 mg/mL/min over a 30-min intravenous infusion on Day 1 of a 21-day cycle. All patients were supplemented with folic acid and vitamin B12 to reduce the hematological toxicity of pemetrexed.nnnRESULTSnThere were one (3.1%) complete response and five partial (15.6%) responses. The overall response rate was 18.8% and the median response duration was 4.4 months. Among the responders, four patients had adenocarcinoma and two had squamous cell carcinoma. Nine patients had stable disease, and the disease control rate was 46.9%. With a median follow up duration of 9.4 months, the median time to progression was 2.3 months and the median OS was 9.4 months. Seven patients (21.9%) experienced grade 3 and 4 hematologic toxicities; one anemia (3.1%), six neutropenia (18.8%), and six thrombocytopenia (18.8%). Two patients experienced grade 4 febrile neutropenia with infection. Four patients (12.5%) experienced grade 3 non-hematologic toxicities; four asthenia (12.5%), two anorexia (6.3%), and one stomatitis (3.1%). Grade 1-2 peripheral neuropathy developed in 13 patients (40.6%).nnnCONCLUSIONnThe combination of pemetrexed and carboplatin showed favorable toxicity profiles and activity in the pretreated patients with advanced NSCLC. It is suggested that this regimen can be a good chemotherapeutic option as a salvage therapy for patients with NSCLC.

Predictors of high score patient-reported barriers to controlling cancer pain: A preliminary report

PurposePain is one of the most common and devastating symptoms in cancer patients, and misunderstandings on the patient’s part can cause major obstacles in pain management.MethodWe evaluated factors associated with patient’s high barrier score to managing cancer-associated pain by having 201 patients complete the Korean Barriers Questionnaire II, the Brief Pain Inventory—Korean, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and the Korean Beck Depression Inventory. The Pain Management Index (PMI) was also assessed.ResultsThe patients were from nine oncology clinics in university hospitals and a veterans’ hospital in South Korea. The median pain score (0–10 scale) was 4, with a median percentage of pain improvement during the last 24xa0h of 70xa0%. A total of 150 patients (75xa0%) received strong opioids, and 177 (88xa0%) achieved adequate analgesia (positive PMI). Mean scores ± SD for the Barriers Questionnaire II ranged from 1.5 ± 1 to 2.8 ± 1.1, with the harmful effects subscale the highest. In the multiple regression model, depression was significantly associated with total barrier score to pain management (p < 0.0001). Pain reduction was significantly associated with the fatalism subscale.ConclusionsDepression was associated with high barrier score in patients with cancer pain. Management of cancer pain should include screening for depression, and management of depression could reduce patient-reported barriers to pain management.

Phase II study of weekly carboplatin and irinotecan as first-line chemotherapy for patients with advanced non-small cell lung cancer

PurposePlatinum-based doublet chemotherapy has a major role in the treatment of patients with advanced non-small cell lung cancer (NSCLC). The weekly fractionated administration of cisplatin for patients with NSCLC has been shown to be active. Irinotecan and carboplatin are effective against NSCLC and demonstrated synergism with non-cross-resistance in preclinical studies. We conducted a phase II study of weekly combination of carboplatin and irinotecan as first-line chemotherapy for patients with advanced NSCLC.MethodsFrom March 2009 to November 2011, 24 patients who were diagnosed with inoperable or metastatic NSCLC were enrolled. Treatment consisted of carboplatin at an AUC 2.5xa0mg/mL/min over 30-min intravenous infusion and irinotecan 65xa0mg/m2 over 90-min intravenous infusion on day 1 and day 8, respectively. The treatment was repeated every 3xa0weeks.ResultsOne patient (4.2xa0%) achieved complete response, and seven (29.2xa0%) showed partial response. Overall response rate was 33.3xa0%, with median response duration of 4.55xa0months. Nine patients had stable disease, and disease control rate was 70.8xa0%. With median follow-up of 12.8xa0months, median progression-free survival was 4.5xa0months (95xa0% CI 1.8–7.2), and median overall survival was 15.5xa0months (95xa0% CI 6.9–24.1). Major toxicity was myelosuppression. Grade 3–4 neutropenia and thrombocytopenia occurred in 50 and 20.8xa0% of patients, respectively. Two patients experienced febrile neutropenia. Non-hematologic toxicities were generally mild. One patient suffered grade 4 diarrhea, and one treatment-related death due to pneumonia was occurred.ConclusionThe weekly combination of carboplatin and irinotecan showed favorable activity and manageable toxicity profiles in chemo-naïve patients with advanced NSCLC. Our results suggest that this regimen can be a reasonable chemotherapeutic option for patients with advanced NSCLC.

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.

Multicenter, cross-sectional observational study of the impact of neuropathic pain on quality of life in cancer patients

PurposeNeuropathic cancer pain (NCP) is a common and potentially debilitating symptom in cancer patients. We investigated the prevalence of NCP, as well as its management and association with QOL.MethodsCancer patients with pain ≥1 on the visual analogue scale (VAS) were surveyed with the Douleur Neuropathique (DN4) questionnaire, the Brief Pain Inventory-Short Form (BPI-SF), and the EuroQOL five dimensions (EQ-5D) questionnaire. The associations between NCP and pain severity or NCP and QOL, while controlling for variables relevant to QOL, were then analyzed.ResultsA total of 2003 patients were enrolled in this survey; the prevalence of NCP was 36.0% (nxa0=xa0722, 95% CI, 32.5–39.5). We found that NCP in cancer patients was closely correlated to a higher pain severity (BPI-SF; 4.96xa0±xa01.94 versus 4.24xa0±xa02.02, pxa0<xa00.001), and in patients with NCP, pain more severely interfered with daily living, as compared to those without NCP (BPI-SF; 4.86xa0±xa02.71 versus 4.41xa0±xa02.87, pxa0<xa00.001). Patients with NCP also had worse QOL than those without NCP, as measured by EQ-5D index score (0.47xa0±xa00.30 vs. 0.51xa0±xa00.30, pxa0=xa00.005), and this was confirmed using multivariate analysis (pxa0<xa00.001), even after controlling for other variables such as age, sex, disease stage, cancer duration, radiotherapy, chemotherapy, and comorbidities. Importantly, adjuvant analgesics were used in less than half of patients with NCP (nxa0=xa0358, 46.4%).ConclusionsWe found that NCP in cancer patients was significantly associated with a worsened QOL, and current management is inadequate. Therefore, future research aimed at developing improved strategies for management of NCP is required.

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.

Phase II study with fractionated schedule of docetaxel and cisplatin in patients with advanced non-small cell lung cancer

BackgroundDocetaxel and cisplatin combination chemotherapy is established first-line chemotherapy for advanced non-small cell lung cancer (NSCLC). We evaluated a weekly schedule of docetaxel and cisplatin for efficacy and tolerability in patients with chemotherapy-naive NSCLC.MethodsPatients enrolled in this study had stage IIIB or IV NSCLC with measurable disease, no prior chemotherapy, and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2. Treatment consisted of docetaxel 40xa0mg/m2 and cisplatin 35xa0mg/m2 given on D1 and D8 every 3xa0weeks. Patients were evaluated for response after every 2xa0cycles of treatment.ResultsThirty six patients were enrolled, and 35 underwent treatment. Of these, 29 were males and 7 females, median age was 61xa0years (range, 38–68). About 31 patients had ECOG PS 0-1 and 4 patients had ECOG PS 2. Fifty seven percentage (20/35) of patients had adenocarcinoma and 74.3% (26/35) had stage IV disease. A total of 153 cycles of chemotherapy were administered. Of the 35 patients treated, 17 (48.6%) achieved partial response, 11 (31.4%) showed stable disease, and 6 (17.1%) had progressive disease. Median duration of response was 5.3xa0months (95% CI: 4.2–6.2xa0months), and median time to disease progression was 4.6xa0months (95% CI: 2.9–6.3xa0months). Estimated overall survival at 1xa0year was 65.7%. The major hematologic toxicity was myelosuppression. Grade 3 or 4 anemia occurred in 6 cycles, and grade 3 or 4 neutropenia was observed in four cycles. Major non-hematologic toxicities were grade 3 nausea in three patients and grade 3 fatigue in two patients. Three patients developed pneumonia and one patient had infectious colitis. There were no treatment-related deaths in this study.ConclusionsWeekly schedule of docetaxel and cisplatin as first-line treatment for NSCLC had good efficacy and manageable toxicity.

Bilateral subdural hemorrhage as a possible adverse event of gefitinib in a patient with non-small cell lung cancer.

Gefitinib, a selective inhibitor of epidermal growth factor receptor tyrosine kinase is an effective agent used in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Adverse drug reactions were frequently observed in the skin, gastrointestinal tract, and liver, but they were generally mild in severity and reversible. Therefore, gefitinib has been regarded as a relatively safe agent. As a serious adverse effect, however, acute lung injury has been reported. The present report describes a patient with NSCLC who developed bilateral subdural hemorrhage as a possible adverse drug reaction after gefitinib therapy. We expect that this case may provide a reference for clinicians being involved in the treatment with gefitinib.

Efficacy and tolerability of ramucirumab monotherapy or in combination with paclitaxel in gastric cancer patients from the Expanded Access Program Cohort by the Korean Cancer Study Group (KCSG)

BackgroundRamucirumab improves survival in gastric cancer patients. The efficacy and safety of ramucirumab outside of a clinical trial were evaluated using an expanded access program (EAP).MethodsAdvanced gastric cancer patients treated with ramucirumab in combination with paclitaxel or with ramucirumab monotherapy in a Korean EAP were evaluated. Baseline characteristics were assessed for progression-free survival (PFS) and overall survival (OS), and adverse events were evaluated according to the treatment regimen.ResultsOf 265 patients, 228 received ramucirumab plus paclitaxel, and 37 received ramucirumab monotherapy. Grade 3 or 4 neutropenia was more common with ramucirumab plus paclitaxel than with ramucirumab monotherapy (46.7 vs. 8.1%). Gastrointestinal (GI) perforation developed in seven patients (3.1%) in the ramucirumab plus paclitaxel group. The overall response and disease control rates were 16.6 and 66.3% in the ramucirumab plus paclitaxel group, and 5.4 and 37.8% in the ramucirumab monotherapy group, respectively. PFS and OS were 3.8 and 8.6xa0months in the ramucirumab plus paclitaxel group, and 1.8 and 6.4xa0months in the ramucirumab monotherapy group, respectively. In multivariate analysis, alkaline phosphatase, albumin, and neutrophil-to-lymphocyte ratio (NLR) were the independent prognostic factors for PFS, while albumin, NLR, number of metastatic sites, and large amount of ascites were independent prognostic factors for OS.ConclusionIn the Korean EAP cohort, ramucirumab showed similar efficacy to the results of the previous trials for gastric cancer. However, the level of GI perforation was slightly increased in the ramucirumab plus paclitaxel group.