In Sil Choi

Predictive and Prognostic Impact of Epidermal Growth Factor Receptor Mutation in Non–Small-Cell Lung Cancer Patients Treated With Gefitinib

PURPOSE This study was undertaken to investigate the effects of epidermal growth factor receptor (EGFR) mutation and its downstream signaling on response and survival in non-small-cell lung cancer (NSCLC) patients treated with gefitinib. PATIENTS AND METHODS For 90 consecutive NSCLC patients who had received gefitinib, EGFR mutation was analyzed by DNA sequencing of exons 18, 19, 21, and 23 in the EGFR tyrosine kinase domain. Expressions of phosphorylated (p) -Akt and p-Erk were determined via immunohistochemistry. Response rate, time to progression (TTP), and overall survival were compared between each group according to EGFR mutation, as well as p-Akt and p-Erk expression. RESULTS Seventeen patients (18.9%; 95% CI, 10.8 to 27.0) harbored EGFR mutations. These mutations include deletions in exon 19 in seven patients, L858R in six patients, G719A in three patients, and a novel A859T in one patient. Response rate in patients with EGFR mutation was 64.7% (11 of 17 patients; 95% CI, 42.0 to 87.4), in contrast to 13.7% (10 of 73 patients; 95% CI, 5.8 to 21.6) in patients without mutation (P < .001). Moreover, these 17 patients with EGFR mutation had significantly prolonged TTP (21.7 v 1.8 months; P < .001) and overall survival (30.5 v 6.6 months; P < .001) compared with the remaining 73 patients without mutation. Although no significant correlation was detected between EGFR mutation and expressions of p-Akt or p-Erk, p-Akt overexpression was associated with prolonged TTP in patients with EGFR mutation. CONCLUSION Our data further support the importance of EGFR mutation with regard to gefitinib sensitivity. In addition to its predictive role, EGFR mutation confers significant survival benefits on NSCLC patients treated with gefitinib.

Efficacy of modified regimen with attenuated doses of paclitaxel plus carboplatin combination chemotherapy in elderly and/or weak patients with advanced non-small cell lung cancer.

PURPOSE We conducted this study to evaluate the activity and toxicity of a combination regimen of paclitaxel plus carboplatin in patients with advanced NSCLC aged 65 years or older and/or in those with an ECOG performance status (PS) 2. MATERIALS AND METHODS Chemotherapy-naive patients with unresectable pathologically-proven NSCLC and of either age >or=65 or ECOG PS 2 were eligible. Patients received modified regimen with attenuated doses of paclitaxel (135 mg/m(2) i.v. for 3 h D1) and carboplatin (AUC=5, D1) every 3 weeks. RESULTS Thirty-five patients were enrolled. Nineteen patients were aged 65 or older (54%) and 26 patients (74%) were ECOG PS 2. The objective response rate was 40% with 14 partial responses. The median time to progression was 22 weeks. Grade 3 leucopenia occurred in 1 cycle and one case of neutropenic fever. CONCLUSIONS The modified regimen with attenuated doses of paclitaxel plus carboplatin combination chemotherapy was effective and well tolerated in patients with advanced NSCLC aged 65 years or older and/or in those with ECOG PS 2.

Reduced Dose Intensity FOLFOX-4 as First Line Palliative Chemotherapy in Elderly Patients with Advanced Colorectal Cancer

To evaluate the toxicity and efficacy of a reduced dose intensity (mini-) FOLFOX-4 regimen as a first-line palliative chemotherapy in elderly patients (≥70 yr of age) with advanced colorectal cancer, data from prospective databases at Seoul National University Bundang Hospital and Seoul Municipal Boramae Hospital were analyzed. A total of 20 patients were enrolled between January 2001 and August 2004, and were treated with oxaliplatin 65 mg/m2 on day 1, and with 2-hr infusions of leucovorin 150 mg/m2 followed by a 5-FU bolus (300 mg/m2) and 22-hr continuous infusions (450 mg/m2) for 2 consecutive days every 2 weeks until progression, unacceptable toxicity or patient refusal. Sixteen patients were evaluable for response with an overall response rate of 43.8%. Median progression-free survival was 4.8 months (95% CI: 3.0-6.7) and overall survival was 13.5 months (95% CI: 11.1-16.0). The main side effects were anemia and neutropenia, which were observed in 20.8% and 17.7%, respectively, of the total cycles administered. There were no grade 4 toxicities and only one patient suffered from febrile neutropenia. No grade 3 toxicities occurred except for anemia (5.2%) and vomiting (1.0%). In conclusion, the mini-FOLFOX-4 regimen was found to be well tolerated with acceptable toxicity, and to provide a benefit for elderly patients with colorectal cancer.

Epidermal growth factor receptor intron 1 CA dinucleotide repeat polymorphism and survival of advanced gastric cancer patients treated with cetuximab plus modified FOLFOX6

(Cancer Sci 2010; 101: 793–799)

Phase II Study of Chemotherapy with ACNU Plus Cisplatin Followed by Cranial Irradiation in Patients with Newly Diagnosed Glioblastoma Multiforme

AbstractPurpose: To evaluate the efficacy and toxicity of chemotherapy with ACNU (1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-(2-chloroethyl)-3-nitrosourea) plus cisplatin followed by cranial irradiation in patients with newly diagnosed glioblastoma multiforme. Patients and methods: Between August 1999 and July 2001, previously untreated 30 patients with histologically confirmed glioblastoma multiforme were treated. Chemotherapy consisting of up to 2 cycles of 72 h of continuous intravenous infusion of ACNU (40 mg/m2/day) and cisplatin (40 mg/m2/d) was given over a 6-week period. Radiation was begun 6 weeks after the second cycle of chemotherapy. Results: Median age was 48 years (range 18–66 years) and 22 patients with residual measurable disease after surgery were eligible for response analysis. One (5%) had a complete response (CR), 36% partial response (PR), 14% stable disease (SD), and 45% progressive disease (PD) after chemotherapy. After additional radiation, 22% had CR, 22% PR, 16% SD, and 42% PD. Grades III and IV leukopenia and thrombocytopenia occurred in 18 cycles (36%) and 15 cycles (30%), respectively. No fatal complications occurred. Median time to progression was 5.9 months (95% CI 5.1–6.8 months) and median overall survival was 14.9 months (95% CI 9.1–20.7 months). Conclusions: Preradiation chemotherapy with ACNU plus cisplatin is effective and feasible in patients with glioblastoma multiforme.

Phase II Study of Low-dose Paclitaxel and Cisplatin as a Second-line Therapy after 5-Fluorouracil/Platinum Chemotherapy in Gastric Cancer

This study was performed to evaluate the efficacy and toxicity of low-dose paclitaxel/cisplatin chemotherapy in patients with metastatic or recurrent gastric cancer that had failed 5-fluorouracil/platinum-based chemotherapy. Thirty-two patients with documented progression on or within 6 months after discontinuing 5-fluorouracil/platinum-based chemotherapy were enrolled. As a second-line treatment, paclitaxel (145 mg/m2) and cisplatin (60 mg/m2) was administered on day 1 every 3 weeks. Among 32 patients enrolled, 8 (25%) responded partially to paclitaxel/cisplatin, 8 (25%) had stable disease, and 14 (44%) had progressive disease. Two patients (6%) were not evaluable. The median time to progression (TTP) and overall survival for all patients were 2.9 months and 9.1 months, respectively. The most common hematologic toxicity was anemia (47%). Grade 3 neutropenia developed in three patients (9%), but no other grade 3/4 hematologic toxicity occurred. The most common non-hematologic toxicities were emesis (31%) and peripheral neuropathy (38%). Three cases (9%) of grade 3/4 emesis and 2 cases (6%) of grade 3 peripheral neuropathy developed. In conclusion, low-dose paclitaxel and cisplatin chemotherapy showed moderate activity with favorable toxicity profiles. However, relatively short TTP of this regimen warrants the development of more effective paclitaxel-based regimens other than combination with cisplatin in these patients as second-line therapies.

Oxaliplatin, 5-FU, Folinic Acid as First-line Palliative Chemotherapy in Elderly Patients with Metastatic or Recurrent Gastric Cancer

PURPOSE We investigated the efficacy and safety of a combination of oxaliplatin, 5-fluorouracil (5-FU), and folinic acid (FA) as first-line palliative chemotherapy for elderly patients with metastatic or recurrent gastric cancer. MATERIALS AND METHODS The study patients were chemotherapy-naïve patients (> 65 years old) with histologically confirmed, metastatic or recurrent gastric cancer. Chemotherapy consisted of oxaliplatin 100 mg/m(2) and FA 100 mg/m(2) (2-hour infusion), and then 5-FU 2400 mg/m(2) (46-hour continuous infusion) every 2 weeks. RESULTS A total of 37 patients were studied between April 2004 and October 2006. Of the 34 evaluable patients, none achieved a complete response (CR) and 14 achieved a partial response (PR), resulting in an overall response rate of 41.2%. The median time to progression (TTP) was 5.7 months (95% CI: 4.2~6.3 months) and the median overall survival (OS) was 9.8 months (95% CI: 4.4~12.0 months). The main hematologic toxicities were anemia and neutropenia, which were observed in 56.7% and 32.4% of the patients, respectively. Grade 3/4 neutropenia was observed in 8.1% of the patients. None of the patients experienced febrile neutropenia. Peripheral neuropathy occurred in 35.1% of the patients and all were grade 1/2. CONCLUSION This oxaliplatin/5-FU/FA regimen showed good efficacy and an acceptable toxicity profile in elderly patients with metastatic or recurrent gastric cancer.

Multicentric Castleman’s disease complicated by tumor lysis syndrome

We report a case of Castleman’s disease that developed tumor lysis syndrome spontaneously and after systemic chemotherapy. A 44-year-old male patient was admitted with a 2-week history of abdominal distension accompanied by dyspnea. Physical examination revealed multiple lymph node enlargements. After admission, spontaneous hemoperitoneum developed and he underwent exploratory laparotomy, with the removal of the ruptured spleen. Pathologic review of the splenic tissue and excised lymph node gave the diagnosis of multicentric Castleman’s disease. He experienced two episodes of tumor lysis syndrome, initially spontaneous and then chemotherapy related, which needed vigorous management including hemodialysis and intensive fluid therapies. To our knowledge, this is the first reported case of Castleman’s disease complicated by tumor lysis syndrome. This suggests that the possibility of tumor lysis syndrome should be considered when treating Castleman’s disease with a large disease burden.

Pleural Effusion in Multiple Myeloma: Characteristics and Practice Patterns

In many Asian countries battling with the double burden of increasing noninfectious diseases on top of infectious diseases, multiple myeloma (MM) patients presenting with pleural effusion (PE) pose a great diagnostic challenge. Thus, we aimed to analyze the clinical features and practice patterns of such patients. This is a multicenter retrospective study of newly diagnosed MM patients between January 2011 and December 2015. Among 575 MM patients diagnosed during the study period, 80 (13.9%) that were associated with PE were identified and analyzed. The most common cause of PE was parapneumonic (25%), followed by reactive (18.8%). Higher CRP levels and leukocytosis were indicators of parapneumonic PE. There were 7 (8.8%) with myelomatous PE and 2 (2.5%) with tuberculosis. Fifty-six patients underwent additional examinations to determine the exact cause of effusion; 28 patients received computed tomography (CT) of the chest, 5 patients underwent thoracentesis/biopsy, and 23 patients underwent both CT and thoracentesis/biopsy. On the other hand, 24 patients did not undergo additional analyses but were treated empirically. Real-world analyses of practice patterns in MM patients with PE showed the suboptimal use of invasive procedures to determine the exact cause of PE. Since reversible causes and tuberculosis pleurisy are not uncommon, invasive procedures should be actively incorporated as needed.

Prognostic Value of Axillary Nodal Ratio after Neoadjuvant Chemotherapy of Doxorubicin/Cyclophosphamide Followed by Docetaxel in Breast Cancer: A Multicenter Retrospective Cohort Study

Purpose The purpose of this study is to investigate the prognostic value of lymph node (LN) ratio (LNR) in patients with breast cancer after neoadjuvant chemotherapy. Materials and Methods This retrospective analysis is based on the data of 814 patientswith stage II/III breast cancer treated with four cycles of doxorubicin/cyclophosphamide followed by four cycles of docetaxel before surgery. We evaluated the clinical significance of LNR (3 categories: low 0-0.20 vs. intermediate 0.21-0.65 vs. high 0.66-1.00) using a Cox proportional regression model. Results A total of 799 patients underwent breast surgery. Pathologic complete response (pCR, ypT0/isN0) was achieved in 129 patients (16.1%) (hormone receptor [HR] +/human epidermal growth factor receptor 2 [HER2] –, 34/373 [9.1%]; HER2+, 45/210 [21.4%]; triple negative breast cancer, 50/216 [23.1%]). The mean numbers of involved LN and retrieved LN were 2.70 (range, 0 to 42) and 13.98 (range, 1 to 64), respectively. The mean LNR was 0.17 (low, 574 [71.8%]; intermediate, 170 [21.3%]; high, 55 [6.9%]). In univariate analysis, LNR showed significant association with a worse relapse-free survival (3-year relapse-free survival rate 84.8% in low vs. 66.2% in intermediate vs. 54.3% in high; p < 0.001, log-rank test). In multivariate analysis, LNR did not show significant association with recurrence after adjusting for other clinical factors (age, histologic grade, subtype, ypT stage, ypN stage, lymphatic or vascular invasion, and pCR). In subgroup analysis, the LNR system had good prognostic value in HR+/HER2–subtype. Conclusion LNR is not superior to ypN stage in predicting clinical outcome of breast cancer after neoadjuvant chemotherapy. However, the prognostic value of the LNR system in HR+/HER2–patients is notable and worthy of further investigation.