Irinotecan and cisplatin demonstrated promising outcomes in extensive-stage small-cell lung cancer. According to the dosage and schedule of irinotecan, efficacy and toxicity profiles showed subtle differences. This study was designed to evaluate efficacy and toxicity of 3-week schedule of irinotecan/cisplatin in patients with previously untreated extensive-stage small-cell lung cancer. The primary objective was to evaluate response rate and secondary objectives were overall survival and progression-free survival. Patients with previously untreated extensive-stage small-cell lung cancer were enrolled. Irinotecan 65 mg m À2 was administered on days 1 and 8 and cisplatin 60 mg m À2 on day 1. Treatment was repeated every 3 weeks. Seven out of 54 patients (13.0%) had complete response, and partial response was observed in 33 (61.1%). The overall response rate was 74.1% (95% CI; 62.0 -82.2%). Stable disease was observed in eight (14.8%) and no progressive disease was observed. After a median follow-up duration of 28.7 months, the median overall survival and progressive-free survival were 13.6 and 6.5 months, respectively. Major grade 3/4 toxicities were neutropenia (50.0%), anorexia (42.6%), diarrhoea (29.6%), fatigue (29.6%) and vomiting (13.0%). There was one treatment-related death owing to pneumonia. Three-week schedule of irinotecan/cisplatin showed effective antitumour activity and moderate toxicities in patients with previously untreated extensive-stage small-cell lung cancer. British Journal of Cancer (2006) (Jemal et al, 2004), and also in Korea (Shin et al, 2004). The proportion of histologic diagnosis with small-cell lung cancer (SCLC) in the United States is approximately 15% of patients with lung cancer (Jemal et al, 2004), and more than half of these patients are diagnosed with extensive-stage disease. Incidence of SCLC had paralleled trends in cigarette smoking, and smoking prevalence for the adult population is relatively high in Korea. During the last decade, most patients with extensivestage SCLC (ES-SCLC) have been treated with etoposide and platinum resulting in a median survival of 8 -10 months (Roth et al, 1992). Although several trials of platinum-based combination chemotherapy were performed, it failed to show a superiority to combination of etoposide and cisplatin (EP) (Mavroudis et al, 2001;Sundstrom et al, 2002).Irinotecan, which inhibits the function of topoisomerase I in cancer cells, demonstrated synergism and non-cross resistance when combined with platinum agents (Fukuda et al, 1996;Masuda et al, 1996). Kudoh et al (1998) reported that combination chemotherapy of irinotecan and cisplatin (IP) in patients with SCLC showed a promising response rate of 84 with 29% of complete responses and median survival over 13 months. Since then, several phase II/III trials of irinotecan-based combination chemotherapy with different dose and schedule were performed with varying results in SCLC patients (Noda et al, 2002;Kudoh et al, 2005;Hanna et al, 2006;Kinoshita et al, 2006;Schmittel et al, 2006). In...

We investigated outcomes according to a new clinical grading system for chronic graft-versus-host disease (chronic GVHD) in 38 patients who developed chronic GVHD after an allogeneic hematopoietic stem cell transplantation. We categorized the patients into three grade groups, namely, grade I, grade II and grade III, according to the presence of three risk factors: extensive skin involvement, thrombocytopenia (TP) and progressive type of onset. Sixteen patients were classified into grade 1, 19 into grade II and three into grade III. The probability of withdrawal of systemic immunosuppression (IST) at 1, 2 and 3 years was 61, 76 and 87%, respectively. Patients with grades 2 or 3 chronic GVHD had prolonged duration of systemic IST compared to grade 1 (P ¼ 0.043). The probability of GVHD-specific survival (GSS) at 5 years was 52%. Twenty-two of 38 patients with chronic GVHD were still alive and the estimated 3-year overall survival (OS) rate was 60%, whereas that for the group with chronic GVHD grade I and grade II þ III was 64 and 48% (Po0.05). Multivariate analysis showed that prior occurrence of acute GVHD, chronic GVHD grade, serum bilirubin over 1.5 mg/dl, date of diagnosis of chronic GVHD (oday 150 versus 4day 150) and transplantation-risk factor were independent prognostic factors for GSS and OS.

Summary:We studied whether the induction of autologous graftversus-host disease (GVHD) has an antileukemic effect and consequently increases the survival of patients undergoing autologous peripheral blood stem cell transplantation (PBSCT). In all, 22 acute myeloid leukemia patients with favorable and intermediate cytogenetic risk, in their first complete remission, were administered cyclosporine c.i.v. from day 0 to day þ 28 at a dose of 3.0 mg/kg per day and interferon-c (IFN-c) at 0.025 mg/m 2 s.c. every other day from day þ 14 to day þ 42 following autologous PBSCT. Natural-killer (NK)-cell activity assays and skin biopsies were performed. Successful engraftment was achieved in all patients at a median of 13 days without significant additional toxicity. Histologically confirmed cutaneous GVHD developed in 12 patients, and NK-cell activity was significantly augmented after autologous PBSCT in those patients (P ¼ 0.03). After a median follow-up duration of 37.7 months (range, 7.3-72.8), the 3-year disease-free survival (DFS) and overall survival (OS) rates were 64.4 and 73.1%, respectively, without significant correlation with GVHD status or augmentation of NK-cell activity. These data suggest that the administration of cyclosporine and IFN-c following autologous PBSCT improves OS and DFS, which may be attributable to the antileukemic effect, although no difference in survival could be demonstrated between cutaneous GVHD-positive and -negative groups. Bone Marrow Transplantation (2003) 32, 889-895. doi:10.1038/sj.bmt.1704251 Keywords: autologous GVHD; autologous stem cell transplantation; interferon-g; cyclosporine; natural-killercell activity; acute myeloid leukemia Clinically beneficial antitumor effects of graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation (BMT) have been reported previously, despite the fact that GVHD is associated with increased morbidity and mortality.1 Unfortunately, only 25% of patients have a suitable donor for allogeneic BMT and the remaining patients are eligible only for autologous stem cell transplantation (SCT) or unrelated-donor BMT. Although unrelated or mismatched-related BMT are associated with potent antitumor effects, many patients still lack a suitable donor or are not suitable candidates. The lack of a graftversus-tumor effect associated with GVHD may at least partly account for the higher relapse rate in autologous SCT patients. 2On the basis of findings that the relapse rate after allogeneic SCT is remarkably lower in patients with GVHD compared with patients who do not develop this syndrome, 1,3,4 the induction of autologous GVHD is one potential approach with which to improve the outcome for autologous SCT. Autologous GVHD can be induced by the administration of cyclosporine A (CsA) for a short period following autologous SCT. [5][6][7] This autoaggression syndrome shares a similar cutaneous pathology with acute GVHD after allogeneic SCT, even though autologous GVHD is milder, involves only the skin, and is self-limiting. Several initial ...