Jaeheon Jeong

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.

Belotecan for relapsing small-cell lung cancer patients initially treated with an irinotecan-containing chemotherapy: A phase II trial

BACKGROUND Belotecan is a topoisomerase I inhibitor. This phase II trial was conducted to evaluate the efficacy and toxicity of belotecan in relapsing small-cell lung cancer (SCLC) patients after irinotecan failure. PATIENTS AND METHODS SCLC patients, who had relapsed at least 3 months after achieving objective response to irinotecan plus platinum chemotherapy, were eligible. Belotecan was administered at a dose of 0.5 mg/m(2)/day for 5 consecutive days every 3 weeks. RESULTS Twenty-seven patients were enrolled in this study. Twenty-five patients were evaluated for response, and 27 patients were evaluated for toxicity and survival. The overall response rate was 22%. The median time to progression was 4.7 months (95% CI, 3.6-5.8 months), and the median overall survival was 13.1 months (95% CI, 10.4-15.8 months). The most frequent grade 3/4 toxicities were neutropenia (93%) and thrombocytopenia (48%). There was one treatment-related death due to pneumonia. CONCLUSION Belotecan showed modest activity and manageable toxicities in relapsing SCLC patients in this study which was conducted in Asia. But further study in Caucasian patients is needed.

Comparison of Long-Term Outcome between Doublet and Triplet Neoadjuvant Chemotherapy in Non-Metastatic Osteosarcoma of the Extremity

Objective: This study compared outcomes between doublet (AP) and triplet (IAP) neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremity. Methods: A total of 124 patients were enrolled. In the AP group, a doublet regimen of intraarterial cisplatin and intravenous doxorubicin was given to 77 patients from 1991 to 1999. In the IAP group, a triplet regimen of additional intravenous ifosfamide was given to 47 patients from 2000 to 2007. After completion of 3 cycles of chemotherapy, patients underwent surgery. We assessed tumor response according to pathologic tumor necrosis, and treated patients with further adjuvant chemotherapy. Results: The overall pathologic response was excellent with more than 90% tumor necrosis in 74.8% of patients. Total necrosis of tumors was also found in 46 (37.4%) patients. There was no difference between the 2 groups in pathologic response (75.3 vs. 72.3%; p = 0.52) or other clinicopathologic parameters. There was no difference between the 2 groups in recurrence rate (31.2 vs. 31.9%; p = 0.17) or lung metastasis (28.6 vs. 23.4%; p = 0.53). Moreover, there were no statistical differences in median disease-free survival and overall survival between the groups. There was more hematologic toxicity in the IAP group (neutropenia, p = 0.002; thrombocytopenia, p = 0.001; febrile neutropenia, p < 0.001). Conclusions: The addition of ifosfamide to doxorubicin and cisplatin in neoadjuvant chemotherapy did not show improved outcomes in this study. Further trials are required to elucidate optimal neoadjuvant chemotherapy and effective salvage regimens.

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.

An Attempt for Combining Microarray Data Sets by Adjusting Gene Expressions

PURPOSE The diverse experimental environments in microarray technology, such as the different platforms or different RNA sources, can cause biases in the analysis of multiple microarrays. These systematic effects present a substantial obstacle for the analysis of microarray data, and the resulting information may be inconsistent and unreliable. Therefore, we introduced a simple integration method for combining microarray data sets that are derived from different experimental conditions, and we expected that more reliable information can be detected from the combined data set rather than from the separated data sets. MATERIALS AND METHODS This method is based on the distributions of the gene expression ratios among the different microarray data sets and it transforms, gene by gene, the gene expression ratios into the form of the reference data set. The efficiency of the proposed integration method was evaluated using two microarray data sets, which were derived from different RNA sources, and a newly defined measure, the mixture score. RESULTS The proposed integration method intermixed the two data sets that were obtained from different RNA sources, which in turn reduced the experimental bias between the two data sets, and the mixture score increased by 24.2%. A data set combined by the proposed method preserved the inter-group relationship of the separated data sets. CONCLUSION The proposed method worked well in adjusting systematic biases, including the source effect. The ability to use an effectively integrated microarray data set yields more reliable results due to the larger sample size and this also decreases the chance of false negatives.

A Locally Advanced Breast Cancer with Difficult Differential Diagnosis of Carcinosarcoma and Atypical Medullary Carcinoma, which had Poor Response to Adriamycin- and Taxane-based Neoadjuvant Chemotherapy: A Case Report

Atypical medullary carcinomas and carcinosarcoma have unique histopathological features. Here we present a case with a breast malignancy that had pathological characteristics of both. A 54-year old patient with a malignant breast mass received 6 cycles of adriamycin-based chemotherapy, followed by 3 cycles of paclitaxel monotherapy, and had a poor clinical response to treatment. A modified radical mastectomy was performed. The pathological diagnosis was complicated by an inability to distinguish between atypical medullary carcinoma and carcinosarcoma. The findings included a tumor that was well-circumscribed, high grade and a syncytial growth pattern as well as biphasic sarcomatous and carcinomatous characteristics. In conclusion, atypical medullary carcinoma and carcinosarcoma of the breast have entirely different prognoses and should be managed differently. Both should be treated by surgical resection, and additional therapy should be considered based on the cancer with the poorer prognosis.

A Randomized, Open-Label, Phase II Study Comparing Pemetrexed Plus Cisplatin Followed by Maintenance Pemetrexed versus Pemetrexed Alone in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Non-small Cell Lung Cancer after Failure of First-Line EGFR Tyrosine Kinase Inhibitor: KCSG-LU12-13

Purpose The optimal cytotoxic regimens have not been established for patients with non-small cell lung cancer (NSCLC) who develop disease progression on first-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Materials and Methods We conducted a multi-center randomized phase II trial to compare the clinical outcomes between pemetrexed plus cisplatin combination therapy followed by maintenance pemetrexed (PC) and pemetrexed monotherapy (P) after failure of first-line EGFR-TKI. The primary objective was progression-free survival (PFS), and secondary objectives included overall response rate (ORR), overall survival (OS), health-related quality of life (HRQOL), and safety and toxicity profiles. Results A total of 96 patientswere randomized, and 91 patientswere treated at 14 centers in Korea. The ORR was 34.8% (16/46) for the PC arm and 17.8% (8/45) for the P arm (p=0.066). With 23.4 months of follow-up, the median PFS was 5.4 months in the PC arm and 6.4 months in the P arm (p=0.114). The median OS was 17.9 months and 15.7 months in PC and P arms, respectively (p=0.787). Adverse events ≥ grade 3 were reported in 12 patients (26.1%) in the PC arm and nine patients (20.0%) in the P arm (p=0.491). The overall time trends of HRQOL were not significantly different between the two arms. Conclusion The outcomes of pemetrexed therapy in NSCLC patients with disease progression after firstline EGFR-TKI might not be improved by adding cisplatin.