Min Chung

Paclitaxel versus docetaxel for advanced gastric cancer : a randomized phase II trial in combination with infusional 5-fluorouracil

Taxanes have clearly demonstrated activities against gastric cancer. We compared the combination of paclitaxel plus 5-fluorouracil (5-FU) (PF) with docetaxel plus 5-FU (DF) as first-line chemotherapy in patients with measurable metastatic gastric cancer. Seventy-seven patients were randomly assigned to receive paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 on day 1, in combination with 5-FU 500 mg/m2 continuous infusion on days 1–5. Treatment was repeated every 3 weeks. Of 314 chemotherapy cycles delivered (median 5 in both groups), dose reduction was required more frequently in the DF group, being 9 and 19%, respectively (P<0.01). PF was associated with, although statistically insignificant, substantially less grade 3 or 4 toxicities than DF (68 versus 85%; P=0.09). Global quality of life was similar in both groups, but substantive differences in many symptom scores including pain, dyspnea, constipation and diarrhea favored PF. There were no significant differences in therapeutic efficacy between PF and DF with respect to response rate (42 versus 33%, respectively; P=0.53), and failure-free (3.6 versus 4.2 months; P=0.92) and overall survival (9.9 versus 9.3 months; P=0.42). Both PF and DF appear to have efficacy against metastatic gastric cancer, with different, but acceptable, safety profiles.

Quality of life in patients with advanced gastric cancer treated with second-line chemotherapy

Objective: Despite many trials of systemic chemotherapy in advanced gastric cancer, treatment after failure with first-line chemotherapy remains controversial. We prospectively assessed quality of life (QL) in gastric cancer patients treated with second-line chemotherapy. Methods: Forty-three patients who received second-line chemotherapy for advanced gastric cancer completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and hospital anxiety and depression scale (HADS) at baseline and at regular intervals during and after chemotherapy. Results: Compliance with QL questionnaire completion decreased to 72% after third cycle of treatment. In general, clinically meaningful improvements compared with baseline (change QLQ-C30 scores ≥10) were seen in a number of domains and items, including global health/QL, emotional function, cognitive function and all of the symptom scales and single items but appetite. There was no difference in QL between responders and non-responders (P=0.473). At baseline, 27 (63%) patients were suspected to have anxiety or depressive disorder (HADS score ≥11), and this incidence decreased after chemotherapy (14.7 vs 9.5; P<0.001). Conclusion: Improvements from baseline in QL measures and HADS scores were demonstrated in patients with advanced gastric cancer, treated with second-line chemotherapy.

A stercoral perforation of the descending colon

This is a case report on a stercoral perforation of the descending colon that was not adequately treated in the first operation. Re-operation was required in order to revise the primary repair site and to remove the impacted fecaloma.

Traumatic pulmonary pseudocysts after blunt chest trauma: Prevalence, mechanisms of injury, and computed tomography findings.

BACKGROUND Traumatic pulmonary pseudocyst (TPP) is a rare complication of blunt chest trauma and closely related with severe injury. However, it has been poorly documented. We present a retrospective review of TPP cases treated at our hospital. METHODS The medical records and chest computed tomography scans of patients with TPP treated from January 2010 to December 2013 were retrospectively studied. RESULTS A total of 978 patients underwent chest computed tomography for blunt chest trauma during the study period, and 81 (8.3%) had a total of 150 TPPs. The most common mechanism of injury was being struck by a motorized vehicle (n = 25, 30.9%). The mean (SD) Injury Severity Score (ISS) of the 81 patients was 33.2 (11.4). The prevalence of TPP was higher in younger patients (p = 0.011), but the total number of fractured ribs was significantly lower (p = 0.001). In a subgroup analysis performed according to pseudocyst location, the intraparenchymal group had more severe injuries than the subpleural group (ISS, 23.3 vs. 32.4, p < 0.001; chest Abbreviated Injury Scale [AIS] score, 3.4 vs. 4.0, p < 0.001; number of associated injuries, 2.9 vs. 4.0, p = 0.001). By multivariate analysis, ISS, age, and number of associated injuries were significantly different in these two groups (p = 0.038, p = 0.006, and p = 0.045, respectively). CONCLUSION The prevalence of TPP among cases of blunt chest trauma was 8.3% and was higher in those struck by a vehicle and younger patients. Intraparenchymal pseudocyst was found to be related to more severe injuries. TPP was a self-limiting condition that does not require specific treatment. LEVEL OF EVIDENCE Prognostic/epidemiologic study, level IV.

Surgical outcome and prognostic factors in patients with gallbladder carcinoma

Backgrounds/Aims Gallbladder carcinoma is usually associated with an unfavorable prognosis, and the clinical outcome has not improved much. This study was conducted to evaluate outcomes with gallbladder carcinoma according to the type of surgery performed, and the prognostic factors for survival. Methods One hundred and six patients with gallbladder carcinoma, who underwent surgery for the purpose of curative resection between January 1999 and June 2012 were reviewed retrospectively. Results Out of 106 patients, curative resection was achieved in 75 (70.8%). The cumulative 1-, 2- and 5-year survival rates of the gallbladder carcinoma patients were 93.4%, 80.9% and 63.0%, respectively. Radical resections, including extended cholecystectomy, were more beneficial for long term survival of patients. The 5-year survival rate in patients who underwent curative resection (56.9%) was significantly higher than in those who underwent palliative resection (0%, p=0.000). Multivariate analysis revealed that curative resection, preoperative CA19-9, T-stage, N-stage and differentiation of histology were independently significant prognostic factors. Conclusions Curative resection and early detection of patients with gallbladder carcinoma were the most important factors for long term survival. Radical resection improves survival for patients with localized gallbladder carcinoma and can help to access exact prognosis and treatments.

Interim analysis from a prospective randomized trial of taxanes plus 5-FU in advanced gastric cancer

4193 Background: Paclitaxel and docetaxel has been shown to be effective in some patients with advanced gastric cancer. We used a randomized phase II design to prospectively compare the toxicity and efficacy of taxanes (paclitaxel or docetaxel) plus 5-FU. METHODS Based on results from our previous phase I study, patients with metastatic or recurrent gastric cancer were randomly assigned to one of two treatments. A 2-stage study design was utilized. In the first stage, 25 patients were randomized to receive paclitaxel 175 mg/m2 or docetaxel 75 mg/m2 in combination with infusional 5-FU 500 mg/m2/day for 5 days. Treatment was repeated every 3 weeks. In the presence of one or more responses observed in each groups, additional 19x2 patients should be enrolled and treated, so that the probability of response rate is 10% or higher. RESULTS Of Among 11 patients assessable for response in the paclitaxel group, 2 (18%) patients responded. With docetaxel, 4 (33%) of 12 assessable patients responded. The median time to treatment failure was 3.5 (paclitaxel) and 4.4 months (docetaxel). In 97 treatment cycles delivered (median: 3 in paclitaxel group, 5 in docetaxel group), dose reduction was required in 31 (32%) cycles and median relative dose intensities for paclitaxel, docetaxel and 5-FU were 89%, 88% and 72%, respectively. One patient in each groups died of toxicity during treatment and there were 30 episodes (31%) of grade 3/4 toxicity primarily stomatitis, asthenia, and neutropenia. CONCLUSIONS The combination with docetaxel and 5-FU suggests a trend towards better tolerability and efficacy. The reasons for the poor results in this patient population are unclear, given the relatively good performance status of the patients studied. Alterations in dosing schedule may be needed to enhance activity with tolerable side effects. No significant financial relationships to disclose.

A Pilot Study of Cisplatin, Irinotecan, Leucovorin and 5-fluorouracil (PILF) Combination Chemotherapy for Advanced Gastric Cancer

PURPOSE Irinotecan, in combination with leucovorin/5-fluorouracil (FU) or with cisplatin, is known to be active for treating advanced gastric cancer (AGC). This pilot study evaluated a novel three-drug combination of irinotecan, leucovorin/FU and cisplatin as a first-line treatment of AGC. The primary endpoint was to assess the feasibility in anticipation of conducting a larger phase II study. MATERIALS AND METHODS Chemotherapy-naive AGC patients received irinotecan 150 mg/m(2) on day 1, and leucovorin 200 mg/m(2) and a 22-h infusion of FU 1000 mg/m(2) on days 1 and 2. Cisplatin 30 mg/m(2) was administered on day 2. Treatment was repeated every 2 weeks until disease progression or unacceptable toxicity. RESULTS Of the 17 eligible patients, two patients had an ECOG performance status of 2 and their median age was 48 years (range: 31 to 69). A total of 117 chemotherapy cycles were delivered (median: 6, range: 1 to 12). The causes of treatment discontinuation were disease progression in 9 patients (53%), refusal (35%) and toxicity (12%). Although grade 3 or 4 neutropenia (41% of patients) was the major toxicity that required dose adjustments, only one episode of febrile neutropenia occurred. Grade 3 or 4 nausea and vomiting, diarrhea and fatigue were observed in 35%, 35% and 29% of patients, respectively. None of the patients died of toxicity during treatment. Of the 16 patients who were evaluable for response, 7 (44%) experienced a partial response. CONCLUSION This novel multi-drug combination was tolerated well in patients with AGC. Based on the encouraging efficacy and tolerability, a randomized phase II study is ongoing in this disease setting.

Phase I dose-escalating study of docetaxel in combination with 5-day continuous infusion of 5-fluorouracil in patients with advanced gastric cancer

BackgroundPublished data suggests that docetaxel combined with 5-fluorouracil (5-FU) may have synergistic activity in treating advanced gastric cancer. We performed a phase I study of docetaxel and 5-FU to determine the maximum tolerated dose (MTD), the recommended dose for phase II studies, and the safety of this combination.MethodsEligible patients had recurrent and/or metastatic advanced gastric cancer with normal cardiac, renal and hepatic function. Traditional phase I methodology was employed in assessing dose-limiting toxicity (DLT) and MTD. On day 1 every 3 weeks, docetaxel 75 mg/m2 (fixed dose) was infused over 1-h, followed immediately by 5-FU as a 5-day continuous infusion.ResultsDose escalation schema was as follows: dose level (DL) 1 (5-FU 250 mg/m2/day), 2 (500), 3 (750), and 4 (1000). Three patients were enrolled on DL1, without DLT. On DL2, 1 DLT (grade 3 stomatitis) was developed in first 3 patients, and this cohort was expanded to 6 patients. Three patients had been enrolled on DL3. Because two out of 3 patients had DLTs, the MTD was reached at DL3.ConclusionThe recommended phase II dose of this combination is 75 mg/m2 docetaxel on day 1 immediately followed by a 5-day continuous infusion of 5-FU 500 mg/m2/day.

A pilot study of low-dose capecitabine plus trastuzumab as first-line treatment for patients older than 75 years with HER2-positive advanced gastric cancer.

165 Background: Elderly patients often present with concomitant co-morbidities and age-associated physiologic problems, such as impaired organ function and functional changes that make the selection of optimal treatment difficult. We report the treatment outcome in 13 elderly patients with HER2-positve advanced gastric cancer who treated with low-dose capecitabine plus trastuzumab. Methods: Patients older than 75 years with gastric cancer were eligible for inclusion if their tumors showed overexpression of HER2 protein by immunohistochemistry (IHC) (3+) or gene amplification by FISH and IHC 2+. Capecitabine 1000 mg/m2was given orally twice a day for 14 days followed by a 1-week rest. Trastuzumab was given by intravenous infusion as a dose of 8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks. Chemotherapy was given every 3 weeks for eight cycles. Results: Between December 2011 and July 2013, 13 consecutive patients (IHC 3+;7, IHC 2+ and FISH+;6) with a median age of 79 years (range, 75...