Ji Eun Uhm

Randomized phase II study of gefitinib versus erlotinib in patients with advanced non-small cell lung cancer who failed previous chemotherapy ☆

PURPOSE Gefitinib and erlotinib are potent EGFR TKIs, with antitumor activity. In this randomized, single-center, non-comparative phase II trial, the efficacy and safety of gefitinib and erlotinib was evaluated as the second-line therapy for advanced non-small cell lung cancer (NSCLC). PATIENTS AND METHODS Patients with locally advanced, metastatic stage IIIB/IV NSCLC who failed first-line chemotherapy and had either EGFR mutation or at least two out of three clinical factors associated with higher incidence of EGFR mutations (female, adenocarcinoma histology, and never-smoker) were eligible. RESULTS A total of 96 (48 per arm) patients were randomly assigned to gefitinib- or erlotinib-arm, respectively. Baseline characteristics were well-balanced between the two arms. The response rates (RR) were 47.9% in the gefitinib arm and 39.6% in the erlotinib arm. Median PFS was 4.9 months (95% CI, 1.3-8.5) in the gefitinib arm and 3.1 months (95% CI, 0.0-6.4) in the erlotinib arm. The most common grade 3/4 toxicity was skin rash. Exploratory analyses showed that there was no significant difference in RR and PFS in the gefitinib arm compared to the erlotinib arm (RR (%) 47.9 vs. 39.6, p=0.269; median survival (months) 4.9 vs. 3.1, p=0.336). There was no significant difference in QOL between the two arms. CONCLUSION Both gefitinib and erlotinib showed effective activity and tolerable toxicity profiles as second-line treatment for the selected population of NSCLC. We may consider conducting a phase III trial to directly compare the efficacy and toxicity between gefitinib and erlotinib in an enriched patient population.

Treatment outcomes and clinicopathologic characteristics of triple-negative breast cancer patients who received platinum-containing chemotherapy.

The aim of this study was to evaluate the role of platinum‐containing chemotherapy for metastatic triple‐negative breast cancer (TNBC) patients in terms of the response rate (RR) and progression‐free survival. A second aim was to characterize the clinical behavior at the time of relapse of TNBC. We retrospectively analyzed the clinical outcomes of patients with metastatic breast cancer who received taxane–platinum chemotherapy as the first‐ or second‐line treatment, focusing on the TN phenotype. In total, 257 patients with metastatic breast cancer received platinum‐containing chemotherapy at Samsung Medical Center from 1999 to 2006. Of these patients, 106 patients with available data on estrogen (ER), progesterone (PgR) and human epidermal growth factor receptor‐2 (HER2) receptor status received taxane–platinum regimen as the first‐ or second‐line treatment. The overall RR of patients with TNBC was 39%. This rate did not differ significantly from those of patients with other phenotypes. The time to death after chemotherapy (19 vs. 50 months, p = 0.037) and overall survival (OS) (21 vs. 56 months, p = 0.030) differed significantly between patients with TNBC and non‐TNBC. TNBC showed a unique locoregional infiltration pattern at relapse, which might reflect its aggressive clinical behavior. Despite the similar response to platinum‐containing chemotherapy, patients with TNBC had a shorter OS than patients with non‐TNBC. The implication of TN phenotype as poor prognostic factor is uncertain, because it needs to be defined whether poor outcome is related to the rapid growing characteristics of tumor itself or the resistance to drug therapy. Further prospective studies are warranted.

Prognostic Factors in Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib: A Retrospective Comparison with Previously Known Prognostic Models

Background: Sorafenib, a multitargeted tyrosine kinase inhibitor, is now the treatment of choice for systemic therapy of patients with advanced hepatocellular carcinoma (HCC). Herein, we present the clinical characteristics and outcomes of patients with advanced HCC who were treated with sorafenib. Methods: Data of 201 sorafenib-treated, metastatic HCC patients were collected from a single institution tumor registry. The primary and secondary endpoints were overall survival (OS) and failure-free survival (FFS). Results: Chronic hepatitis B was the predominant cause of HCC (84%). Of 162 evaluable patients, 4 partial responses were recorded. With a median follow-up of 15.7 months, the median FFS and OS were 2.5 months (95% CI 2.3–2.7) and 5.3 months (95% CI 4.4–6.3), respectively. In multivariate analysis, the prognostic factors associated with FFS were the presence of ascites, portal venous thrombosis, serum α-fetoprotein ≧400 ng/ml, albumin, bilirubin, tumor size and number, and performance status. Likewise, the presence of ascites, portal venous thrombosis, tumor size and number, performance status and baseline levels of α-fetoprotein, albumin and bilirubin were significantly related with OS. After adjusting for performance status, the Cancer of the Liver Italian Program scoring system and Okuda stages can better predict the hazard of failure or death than the Child-Pugh classification. Conclusions: Our results suggest that Cancer of the Liver Italian Program scores or Okuda stages, along with performance status, can be useful in stratifying patients with advanced HCC treated with sorafenib.

Favorable response to doxorubicin combination chemotherapy does not yield good clinical outcome in patients with metastatic breast cancer with triple-negative phenotype.

BackgroundWe analyzed the responses to first line treatment and clinical outcomes of metastatic breast cancer patients treated with palliative doxorubicin/cyclophosphamide (AC) according to molecular cancer subtype.MethodsA retrospective analysis was performed for 110 metastatic breast cancer patients selected on the basis of palliative AC treatment and the availability of immunohistochemical data for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2/neu) status.ResultsOf the 110 patients analyzed, 71 (64.5%) were hormone receptor positive (HR+), 14 (12.7%) were HER2+, and 25 (22.7%) were triple negative (TN). There were no differences in age, stage at diagnosis, total number of cycles of palliative chemotherapy, incidence of visceral metastasis, and metastatic sites with the exception of liver among breast cancer subtypes. The overall response rates to AC were 55.9% for the HR+ subgroup, 42.9% for the HER2+ subgroup, and 56.5% for the TN subgroup. The progression-free survival (PFS) in patients with HER2+ and TN were significantly shorter than in the HR+ (median PFS, 9.1 vs 8.1 vs 11.5 months, respectively; p = 0.0002). The overall survival (OS) was 25.4 months in the TN subgroup and 27.3 months in HER2+ subgroup. The median OS for these two groups was significantly shorter than for patients in the HR+ subgroup (median, 38.5 months; 95% CI, 30.1-46.9 months; p < 0.0001).ConclusionsThe response to palliative AC chemotherapy did not differ among breast cancer subtypes. Despite chemosensitivity for palliative AC, the TN subtype has a shorter overall survival than non-TN subtypes. Innovative treatment strategies should be developed to slow the course of disease.

A retrospective study to compare two methotrexate-based regimens for primary central nervous system lymphoma

A retrospective analysis to compare the treatment outcomes of two regimens with different doses of methotrexate (MTX). Seventy-two patients, newly diagnosed with primary central nervous system lymphoma between 1995 and 2006, were included. All patients were treated with one of the two different MTX regimens depending on when the diagnosis was made. Thirty-six patients diagnosed between 1995 and 2002 were treated with 1 g/m2 of intravenous MTX (HD-MTX 1 g/m2, cohort 1). The other 36 patients, diagnosed between 2003 and 2006, received 3.5 g/m2 of intravenous MTX (HD-MTX 3.5 g/m2, cohort 2). The median age was 47 years (range, 17–78 years) and 42 patients (58.3%) were male. The median overall survival (OS) and progression-free survival (PFS) of all patients was 90.3 and 52.9 months, respectively. Although OS and PFS was not statistically different between the two cohorts, cohort 2 achieved higher complete response/unconfirmed complete response rates than cohort 1 at an evaluation conducted between completion of intravenous MTX therapy and the initiation of radiotherapy (52.8% vs. 16.7%, respectively; p = 0.005). Furthermore, there were no deaths within 6 months of MTX therapy for the cohort 2, whereas there were eight deaths by 6-months for cohort 1 (p = 0.003). Even though cohort 2 failed to show superior survival outcomes compared with cohort 1 after sequential brain radiotherapy and intravenous cytarabine, the higher early CR/CRu rate of cohort 2 compared with cohort 1 might indicate that a high dose of MTX is desirable.

Irinotecan and oxaliplatin combination as the first-line treatment for patients with advanced non-small cell lung cancer

BackgroundWe conducted a prospective phase II trial of IrOx in patients with advanced non-small cell lung cancer to evaluate the efficacy and toxicity.Patients and methodsPatients with histologically or cytologically proven non-small cell lung cancer (NSCLC), aged ≥18 years, Eastern Cooperative Oncology Group performance status 0–1, at stage IIIB (pleural effusion)/IV or with recurrent disease not suitable for primary surgical treatment, with no palliative chemotherapy or radiotherapy to the chest or immunotherapy or biologic therapy, the presence of measurable disease by RECIST, and who had given signed written informed consent, were eligible. Treatment consisted of irinotecan 65 mg/m2 on days 1 and 8 and oxaliplatin 130 mg/m2 on day 1, repeated every 3 weeks.ResultsA total of 18 patients were enrolled in June and August 2007, the median age was 59 years (47–73). In total, 71 cycles were administered with a median of 4 cycles per patient (range, 1–6 cycles) and 18 patients were evaluable for treatment response. An independent review of tumor responses gave an overall response rate of 27.7% (CR: 0, PR: 5/18; 95% CI, 7–48.4%) by intent-to-treat analysis. The median overall survival of all patients was 14 months and the median time-to-progression was 4.2 months (95% CI, 1.959–6.441). The most common grade 3/4 toxicities were diarrhea (7% of all cycles) and neutropenia (5.6% of all cycles). Grade 3 peripheral neuropathy occurred in one patient and one patient died due to sepsis.ConclusionThis study suggests that IrOx combination therapy has moderate activity with a tolerable toxicity profile. However, it was not warranted to evaluate further this regimen as first-line treatment for patients with advanced or metastatic NSCLC using the current dosages and schedule.

Analysis of Prognostic Factors of Pediatric-Type Sarcomas in Adult Patients

Objective: Pediatric-type sarcomas such as Ewing’s sarcoma (EWS)/primitive neuroectodermal tumor family and rhabdomyosarcoma are relatively uncommon in adult patients. Optimal treatment strategies for this population and prognosis in adult patients compared with pediatric patients remain controversial. Methods: We retrospectively reviewed pediatric-type sarcoma patients older than 15 years at a single institution. Results: A total of 84 consecutive patients between 1995 and 2009 were identified at the Samsung Medical Center, Seoul, Korea. Median age was 30 years with a range of 15–74 years. Forty-seven patients (56.0%) were diagnosed with Ewing’s sarcoma/primitive neuroectodermal tumor family, 34 (40.5%) with rhabdomyosarcoma and 3 (3.6%) with desmoplastic round-cell tumor. Median follow-up duration was 5.9 years. Median overall survival for all patients was 33.1 months (95% CI 13.5–52.7) and median event-free survival for all patients was 14.4 months (95% CI 5.9–22.9 months). Multivariate analysis revealed that localized disease was a significant independent prognostic factor for longer overall survival (hazard ratio 0.30, 95% CI 0.14–0.66, p = 0.003), and favorable primary tumor sites were associated with longer event-free survival (hazard ratio 0.33, 95% CI 0.11–0.98, p = 0.045). Conclusion: We identified the prognostic variables which may facilitate risk-adapted therapies for this rare adult sarcoma group, which should be further investigated.