Moonjin Kim

A multicenter, phase II trial of everolimus in locally advanced or metastatic thyroid cancer of all histologic subtypes

BACKGROUND This phase II study investigated the efficacy and safety of everolimus, an inhibitor of mammalian target of rapamycin (mTOR), in locally advanced or metastatic thyroid cancer. PATIENTS AND METHODS Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I received everolimus 10 mg daily orally until unacceptable toxicity or disease progression. The primary end point was disease control rate [partial response (PR) + stable response ≥12 weeks]. Secondary end points included response rates, clinical benefit (PD + durable stable disease (SD)], progression-free survival (PFS), overall survival, duration of response, and safety. RESULTS Thirty-eight of 40 enrolled patients were evaluable for efficacy. The disease control rate was 81% and two (5%) patients achieved objective response; their duration of response was 21+ and 24+ weeks. Stable disease (SD) and progressive disease was reported in 76% and 17% of patients, respectively. Seventeen (45%) patients showed durable SD (≥24 weeks) and clinical benefit was reported in 19 (50%) patients. Median PFS was 47 weeks [95% confidence interval (CI) 14.9-78.5]. Calcitonin, CEA, and thyroglobulin concentrations were ≥50% lower than baseline in three (30%) and four (44%) patients with medullary thyroid cancer and five (33%) patients with PTC, respectively. The most common treatment-related adverse events were mucositis (84%), anorexia (44%), and aspartate transaminase/alanine transaminase elevation (26%). CONCLUSIONS Everolimus had a limited activity with low response rate in locally advanced or metastatic thyroid cancer. Reasonable clinical benefit rate and safety profile may warrant further investigation. CLINICALTRIALSGOV NUMBER NCT01164176.

Weekly docetaxel and gemcitabine in previously treated metastatic esophageal squamous cell carcinoma

AIM To assess the efficacy and safety of weekly docetaxel plus a fixed-dose rate (FDR) of gemcitabine in metastatic esophageal squamous cell carcinoma (SCC). METHODS A multi-center, open-label, prospective phase II study was designed. Thirty-three esophageal SCC patients with documented progression after fluoropyrimidine/platinum-based first-line chemotherapy were enrolled and treated with docetaxel 35 mg/m(2) and gemcitabine 1000 mg/m(2) iv at a FDR (10 mg/m(2) per minute) on days 1 and 8. Treatment was repeated every twenty-one days until disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was response rate (RR), and secondary endpoints were safety, progression-free survival (PFS) and overall survival (OS). RESULTS Combination of weekly docetaxel and FDR gemcitabine was well tolerated: the most common treatment-related adverse events were anemia (97%), fatigue (64%) and neutropenia (55%). One patient with multiple lung and lymph node metastases died of respiratory failure after receiving four cycles of chemotherapy, and the possibility of drug-induced pneumonitis could not be completely excluded. Disease control (objective response plus stable disease) in the ITT population was achieved in 88% of patients, and the overall RR was 30% (95%CI: 15%-46%). The median PFS and OS were 4.0 (95%CI: 3.4-4.6) and 8.8 mo (95%CI: 7.8-9.8 mo), respectively. CONCLUSION A combination of weekly docetaxel and FDR gemcitabine showed promising antitumor activity and tolerability in previously treated, metastatic esophageal SCC.

Impact on Survival of Regular Postoperative Surveillance for Patients with Early Breast Cancer

Purpose The purpose of this study is to evaluate the role of regular postoperative surveillance to improve the prognosis of patients with breast cancer after curative surgery. Materials and Methods We retrospectively analyzed the medical records of 4,119 patients who received curative surgery for breast cancer at Samsung Medical Center between January 2000 and September 2008. Patients were divided into two groups (group I, regular postoperative surveillance; group II, control group) according to their post-therapy follow-up status for the first 5 years after surgery. Results Among the 3,770 patients selected for inclusion, groups I and II contained 3,300 (87%) and 470 (13%) patients, respectively. The recurrence rates at 5 years for groups I and II were 10.6% and 16.4%, respectively (hazard ratio, 0.85; 95% confidence interval [CI], 0.67 to 1.09; p=0.197). The 10-year mortality cumulative rates were 8.8% for group I and 25.4% for group II (hazard ratio, 0.28; 95% CI, 0.22 to 0.35; p < 0.001). In multivariate analysis for recurrence-free survival (RFS), age over 40 years (p < 0.001), histologic grade 1 (p < 0.001), and pathologic stage I (p < 0.001) were associated with longer RFS but not with follow-up status. Multivariate analysis for overall survival (OS) revealed that patients in group I showed significantly improved OS (hazard ratio, 0.29; 95% CI, 0.23 to 0.37; p < 0.001). Additionally, age over 40 years, histologic grade I, and pathologic stage I were independent prognostic factors for OS. Conclusion Regular follow-up for patients with breast cancer after primary surgery resulted in clinically significant improvements in patient OS.

Are there any candidates for adjuvant hysterectomy among patients with locally advanced bulky cervical cancer initially treated with cisplatin-based chemoradiation?

e15504 Background: Locally advanced bulky cervical cancer (LABCC) is characterized by poor local control. The objective of this study was to identify the clinicopathologic variables associated with 1-year central-only recurrence, which will serve as criteria for adjuvant hysterectomy after radiation (AHR) in patients with LABCC. METHODS Between January 2000 and August 2007, we retrospectively evaluated outcomes in 225 patients with LABCC who were initially treated with radiation or chemoradiation. RESULTS Among the 225 patients with LABCC, there were 41 recurrences within 1 year following treatment (8 central-only and 33 pelvis and/or distant site recurrences). Age, stage, and treatment type were not associated with the 1-year central-only recurrences; however, tumor size ≥ 8 cm had a statistically significant association based on multivariate analysis (OR, 5.39; 95% CI, 1.15-25.31; p=0.03). The combination of non-squamous cell (non-SCC) type and tumor size ≥ 8 cm had a significantly higher recurrence within 1 year (OR, 43.0; 95% CI, 4.78-386.68; p < 0.01). CONCLUSIONS Of patients with LABCC, those with non-SCC tumors ≥ 8 cm in size were at high risk for early central-only recurrence after cisplatin-based chemoradiation and represent the subset of patients for whom AHR is beneficial.

Paclitaxel and cisplatin combination chemotherapy for advanced gastric cancer failed to 5-fluorouracil-based chemotherapy.

Background :There is no effective treatment in patients with advanced gastric cancer failed to first - line chemotherapy. Taxane is one of new drugs identified as having substantial activity in gastric cance. We performed a phase II trial to evaluate the efficacy and toxicity of docetaxel plus cisplatin regimen as a salvage chemotherapy for advanced gastric cancer failed to 5- fluorouracil (5-FU)-based chemotherapy. Methods : Metastatic or recurrent gastric cancer patients failed to 5-FU-based regimen with an Eastern Cooperative Oncology Group (ECOG) were eligible in this trial. Docetaxel (60 mg/m) was infused over 1 hour, before cisplatin (60 mg/m) infused over 2 hours on day 1, once every 3 weeks until disease progression or unacceptable toxicity was detected. Response to treatment was assessed every two or three cycles. Results : From October 1999 to December 2000, forty-one patients were enrolled in this study. Twenty-eight of forty-one patients were assessable for response. Partial response was observed in seven patients and stable disease in four patients. The response rate was 25.0% (95% confidence interval: 20.4-29.6%) and median duration of response was 22 weeks (range: 11-53 weeks). The median survival of all enrolled patients was 24 weeks (range: 7-65 weeks). For a total of 112 cycles of chemotherapy, grade 3 and 4 toxicity was 8.9% for neutropenia, 4.5% for nausea/vomiting and 1.8% for mucositis. Conclusion :Salvage chemotherapy with docetaxel plus cisplatin regimen in gastric cancer was active with acceptable toxicities.