Prevalence, course and factors associated with delirium in elderly patients with advanced cancer: a longitudinal observational study.

OBJECTIVE: The aim of this study was to investigate the prevalence of delirium on admission, the course of delirium during a 2-week period after admission and factors associated with delirium on admission, among elderly patients with advanced cancer. METHODS: Patients aged ≥ 65 years with incurable lung or gastroenterological cancer and the Eastern Cooperative Oncology Group Performance Status 2 or greater were continuously sampled after admission to a university hospital. Participants were evaluated for DSM-IV-TR delirium by trained psychiatrists and the delirium subtype was assessed using the Delirium Motor Subtype Scale within 4 days after admission and again 2 weeks later. In addition, we assessed associated factors with delirium on admission. RESULTS: Among 73 eligible patients, complete data were available from 61 on admission and 49 after 2 weeks. Twenty-six patients (43%) met delirium criteria on admission (hypoactive: 58%, unspecified: 35%, hyperactive: 4%, mixed: 4%). Of these, 19 (73%) remained delirious 2 weeks later. Of 35 patients without delirium on admission, 21 (60%) remained delirium-free 2 weeks later and 7(20%) became delirious. Overall, 33/61 (54%) developed delirium at some point during the study. Patients receiving steroids at admission were more likely to have delirium (odds ratio = 5.0; 95% confidence interval = 1.5-16). CONCLUSIONS: Given the high prevalence of the delirium, all patients with advanced cancer should be screened for delirium both on admission and regularly thereafter. In addition, medical staff should be aware that steroid use on admission is an additional indicator of elevated risk for delirium.

Significance of c-MET overexpression in cytotoxic anticancer drug-resistant small-cell lung cancer cells.

The c-MET receptor tyrosine kinase is the receptor for hepatocyte growth factor. Recently, activation of the c-MET/hepatocyte growth factor signaling pathway was associated with poor prognosis in various solid tumors and was one of the mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib. But the link between c-MET activation and the cytotoxic anticancer drug has not been fully examined. Here, we found that the enhanced expression and activation of c-MET in cytotoxic anticancer agent-resistant small-cell lung cancer cells. Downregulation of c-MET expression by siRNA against the c-MET gene or inhibition of c-MET activation by SU11274, a c-MET inhibitor, in the resistant cells altered resistance to the cytotoxic anticancer agent. These results indicated that c-MET overexpression might play an important role in acquired resistance to cytotoxic anticancer drugs. Furthermore, the number of c-MET gene loci was increased in the resistant cells compared to the parental cells. In conclusion, increased c-Met expression through an increase in the number of c-MET gene loci is one of the mechanisms of acquired resistance to cytotoxic anticancer drugs. Our results add a new strategy, the targeting of c-MET, for overcoming resistance to cytotoxic agents in small-cell lung cancer.

Transformed lymphoplasmacytic lymphoma involving the main carina: A case report.

A 41-year-old male was admitted to Nagoya City University Hospital subsequent to experiencing a cough with bloody sputum for a few days. The patient had a 4-year history of lymphoplasmacytic lymphoma (LPL) and had achieved a good partial response to anticancer chemotherapy. Chest computed tomography (CT) showed an endobronchial tumor of the main carina. A bronchoscopy revealed an exophytic tumor at the main carina, and autofluorescence imaging bronchovideoscopy showed that the tumor and surrounding area were magenta in color. The biopsy specimens demonstrated that the endobronchial tumor was composed of large atypical lymphoid cells. The patient was diagnosed with a high-grade transformation of LPL. In addition to describing a rare case of transformed LPL involving the main carina, the present study also summarizes and discusses endobronchial lymphomas, with a brief review of a number of published studies.

Thymidylate synthase gene copy number as a predictive marker for response to pemetrexed treatment of lung adenocarcinoma.

BACKGROUND: Pemetrexed is a key drug for therapy of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: In a search for biomarkers for study of the efficacy of pemetrexed treatment, we examined the thymidylate synthase (TYMS) copy number in NSCLC cell lines and in clinical NSCLC samples treated with pemetrexed, combined with platinum drugs. RESULTS: TYMS copy numbers in lung adenocarcinoma cell lines were significantly lower than in squamous cell carcinoma (p=0.0105), and a significant correlation was found between the TYMS copy number and the 50% inhibitory concentration value for pemetrexed in all 17 lung cancer cell lines tested (r=0.6814, p=0.0026). Moreover, TYMS copy number was significantly lower in clinical NSCLC samples responsive to treatment with pemetrexed combined with platinum drugs (p=0.0067). Furthermore, the decrease in the baseline CT size measurement of pemetrexed combined with platinum drug treatment correlated significantly with TYMS copy number (r=0.7967, p=0.0011). CONCLUSION: To our knowledge, this is the first report of a significant association between TYMS copy number and response to pemetrexed treatment in tumor biopsy specimens. Our results suggest that TYMS copy number could be a predictive biomarker for pemetrexed based chemotherapy.

Involvement of intermediate filament nestin in cell growth of small-cell lung cancer.

BACKGROUND: Nestin is a class VI intermediate filament protein expressed in stem/progenitor cells during the development of the central nervous system. Nestin is detected in various types of tumors and is involved in malignant processes. This study investigated the expression and function of nestin in small-cell lung cancer (SCLC). METHODS: Expression of nestin and achaete-scute homolog 1 (ASH1) was studied in 21 lung cancer cell lines. To assess the function of nestin, a short hairpin RNA (shRNA) targeting nestin was transfected into two SCLC cell lines (DMS53 and SBC3), and cloned cells that showed apparent down-regulation of nestin were obtained. Nestin expression was also studied immunohistochemically in surgically resected SCLC primary tumors and metastatic SCLC tumors obtained from autopsy cases. RESULT: Nestin was expressed in nine of 10 SCLC cell lines. The nestin expression level was significantly higher in SCLC cell lines than in NSCLC cell lines (P < 0.01). There was a statistically significant positive correlation between the expression levels of nestin and ASH1 in SCLC cell lines. Nestin knock-down cells created by transfection with shRNA exhibited decreased invasion and cell proliferation capabilities. Furthermore, nestin was detected in SCLC tumor cells and tumor vessels in all clinical tumor specimens. CONCLUSION: Nestin is expressed in SCLC in association with neuroendocrine features and participates in malignant phenotypes, including cell growth. Therefore, nestin may be a novel therapeutic target for SCLC.

Histology and smoking status predict survival of patients with advanced non-small-cell lung cancer. Results of West Japan Oncology Group (WJOG) Study 3906L.

INTRODUCTION: Smoking status is one of the prognostic factors in advanced non-small-cell lung cancer (NSCLC). Currently, adenocarcinoma (Ad) histology is considered a predictive factor in advanced NSCLC. We investigated the correlation between histology or smoking status and survival of NSCLC patients receiving chemotherapy. METHODS: We retrospectively reviewed clinical data from stage IIIB or IV NSCLC patients who started first-line chemotherapy at affiliated institutions of West Japan Oncology Group from 2004 to 2005. We also collected information on pack-years of cigarette smoking and years since cessation. Overall survival was compared using log-rank test, and Cox regression analysis was used to identify independent prognostic factors. RESULTS: In total, 2542 consecutive patients were enrolled at 40 institutions. Of those, 71 were excluded because of unknown smoking history. The median overall survival of nonsmoking Ad patients (593 days) was longer than that of smoking Ad, nonsmoking non-Ad, and smoking non-Ad patients (384, 374, and 319 days, respectively; p < 0.001). In Cox regression with sex, age, stage, performance, and treatment as covariates, we found significant interaction (p = 0.039) between histology (Ad/non-Ad) and smoking status (smoker/nonsmoker); smoking conferred a hazard ratio of 1.34 (95% confidence interval, 1.15-1.55) in Ad, but only 0.99 (0.75-1.31) in non-Ad. Higher pack-years and shorter period since cessation were significantly associated with poorer survival in Ad (p < 0.001), but not in non-Ad (p ≥ 0.434). CONCLUSION: Ad histology is associated with better prognosis, and only smoking status had a prognostic impact in Ad.

Analgesic effect of switching from oral opioids to a once-a-day fentanyl citrate transdermal patch in patients with lung cancer.

A new once-a-day fentanyl citrate transdermal patch was developed in Japan. We retrospectively investigated analgesic and adverse effects of this drug in 24 patients with lung cancer. All patients were started on this patch by switching from an oral opioid. The mean pain score before switching was 2.45 (0-5); 48 hours after switching, 15 of the 24 patients showed a decreased pain score and the mean score (2.00) was significantly lower than that before switching. Of the 16 patients who had adverse effects of oral opioids, 7 patients showed improvement in their symptoms after switching. Two patients showed adverse effects of the drug but their symptoms were mild, and no patient required dose decrease. This new transdermal patch could be a useful treatment option for cancer pain.

Diagnosis of ovarian cancers using thoracoscopy: Three case reports and review of the literature.

Thoracoscopy is a useful method for diagnosing plural lesions. We diagnosed 3 cases of ovarian adenocarcinoma by thoracoscopy. All patients were middle-aged and elderly women. Initial examination revealed intrathoracic lesions including pleural effusion, but intraperitoneal lesions were unclear. In all cases, adequate samples of tumor cells obtained using thoracoscopy were used in the identification of tumor origin. Elevated serum levels of cancer antigen 125 (CA-125) and Krebs von den lungen-6 (KL-6) were observed in 2 of the 3 patients. Diagnoses of ovarian cancer were based on immunohistochemical examinations and clinical course. This report describes the diagnostic usefulness of thoracoscopy and serum KL-6 in cases of ovarian cancer with predominantly intrathoracic lesions.

Preclinical rationale for synergistic interaction of pemetrexed and cytotoxic nucleoside analogues.

Cytotoxic nucleoside analogues are widely used in cancer chemotherapy. We used the cytosine arabinoside (Ara-C)-resistant erythroleukaemia cell line K562 and the Ara-C-sensitive myeloid leukaemia cell line HL60 to examine the differential expression of molecular markers. We found increased expression levels of deoxycytidine kinase (dCK) and human equilibrative nucleoside transporter 1 (hENT1) and decreased levels of multidrug resistance protein 5 (ABCC5) and ribonucleoside reductase subunit M1 (RRM1) expression in Ara-C-sensitive HL60 cells. We previously established the pemetrexed (MTA)-resistant small cell lung cancer cell lines PC6/MTA-0.4 and PC6/MTA-1.6 and found that MTA-resistant cells are more sensitive to gemcitabine (GEM) and Ara-C compared with parental PC-6 cells. We examined the molecular markers for GEM and Ara-C sensitivity in MTA-resistant cells and found increased gene expression of dCK and hENT1. Furthermore, treatment with MTA resulted in increased expression of dCK and hENT1 and decreased expression of ABCC5 and RRM1, concomitant with the alteration of the resistance to Ara-C in Ara-C-resistant K562 cells. These results provide evidence that the chemotherapeutic activity of the combination of MTA and cytotoxic nucleoside analogues is synergistic with regard to the alteration of metabolic molecules.

A case of carcinomatous meningitis despite prophylactic cranial irradiation in small cell lung cancer during treatment with amrubicin.

A 47-year-old man was diagnosed with limited-disease small cell lung cancer. Treatment was initiated with concurrent chemotherapy and radiotherapy. A partial response was achieved, and prophylactic cranial irradiation (PCI) was administered. Local recurrence was identified on follow-up and treated with amrubicin (AMR). After two courses of AMR, a state of stable disease was achieved and AMR treatment was continued. After the third course of AMR, the patient was urgently hospitalized suffering from a headache and disturbance of consciousness, and a diagnosis of carcinomatous meningitis was made. This case report concerns a case of carcinomatous meningitis despite PCI during treatment with AMR.

S-1 monotherapy for previously treated non-small cell lung cancer: A retrospective analysis by age and histopathological type.

S-1, an oral fluoropyrimidine derivative, has been approved for the treatment of non-small cell lung cancer (NSCLC) in Japan. In the present study, the efficacy and safety of S-1 monotherapy for elderly patients with previously treated NSCLC were retrospectively evaluated, and the efficacy of S-1 monotherapy was compared by histopathological type. This retrospective study included 54 patients with advanced or recurrent NSCLC who had received S-1 monotherapy following the failure of previous chemotherapy regimens at our institutes. Patient outcomes were compared based on their age and histopathological type. S-1 was administered orally, twice daily, while the duration and interval were modified according to the medical condition of each patient. The default delivery schedule, the mean number of S-1 cycles, did not differ significantly between the two age groups (<70 and ≥70 years). The rate of therapy discontinuation, schedule modification or dose reduction due to intolerable toxicities or patient refusal was relatively frequent in the older group (40.7 and 55.6% for ages <70 and ≥70 years, respectively; p=0.414), and the incidence of grade 3 anemia was relatively high in the older group (3.7 and 18.5%, respectively; p=0.192). The response rates (13.0 and 4.8%, respectively; p=0.609) and disease control rates (39.1 and 33.3%, respectively; p=0.761) did not differ significantly between the two age groups. According to histopathological type, the disease control rate was significantly higher in adenocarcinoma (57.9%) compared to non-adenocarcinoma (20.0%, p=0.013). Thus, S-1 monotherapy may be equally effective and tolerated in patients <70 years and those ≥70 years. Additionally, adenocarcinoma may have a higher disease control rate than non-adenocarcinoma.

C609T polymorphism of NAD(P)H quinone oxidoreductase 1 as a predictive biomarker for response to amrubicin.

INTRODUCTION: Amrubicin is a promising agent in the treatment of lung cancer, but predictive biomarkers have not yet been described. NAD(P)H:quinone oxidoreductase 1 (NQO1) is an enzyme known to metabolize amrubicinol, the active metabolite of amrubicin, to an inactive compound. We examined the relationship between NQO1 and amrubicinol cytotoxicity. METHODS: Gene and protein expression of NQO1, amrubicinol cytotoxicity, and C609T single-nucleotide polymorphism of NQO1 were evaluated in 29 lung cancer cell lines: 14 small cell lung cancer (SCLC) and 15 non-SCLC (NSCLC). The involvement of NQO1 in amrubicinol cytotoxicity was evaluated by small interfering RNA against NQO1. RESULTS: A significant inverse relationship between both gene and protein expression of NQO1 and amrubicinol cytotoxicity was found in all cell lines. Treatment with NQO1 small interfering RNA increased amrubicinol cytotoxicity and decreased NQO1 expression in both NSCLC and SCLC cells. Furthermore, cell lines genotyped homozygous for the 609T allele showed significantly lower NQO1 protein expression and higher sensitivity for amrubicinol than those with the other genotypes in both NSCLC and SCLC cells. CONCLUSIONS: NQO1 expression is one of the major determinants for amrubicinol cytotoxicity, and C609T single-nucleotide polymorphism of NQO1 could be a predictive biomarker for response to amrubicin treatment.

Over-expression of MDR1 in amrubicinol-resistant lung cancer cells.

PURPOSE: Amrubicin, a totally synthetic 9-aminoanthracycline anticancer drug, has shown promising activity for lung cancer, but little is known about the mechanism of resistance for this agent. This study was aimed to clarify the role of P-glycoprotein (P-gp) in amrubicinol, an active metabolite of amrubicin, resistance in lung cancer cells. METHODS: Amrubicinol-resistant cell line PC-6/AMR-OH was developed by continuously exposing the small-cell lung cancer cell line PC-6 to amrubicinol. Gene expression level of MDR1, which encodes P-gp, and intracellular accumulation of amrubicinol were evaluated by PC-6 and PC-6/AMR-OH cells. The involvement of MDR1 in amrubicinol resistance was evaluated by treatment with P-gp inhibitor verapamil and small interfering RNA (siRNA) against MDR1. Also, expression levels and single-nucleotide polymorphisms (SNPs) of MDR1 in 22 lung cancer cell lines were examined, and the relationships between these factors and sensitivity to amrubicinol were evaluated. RESULTS: The MDR1 gene was increased approximately 4,500-fold in PC-6/AMR-OH cells compared with PC-6 cells, and intracellular accumulation of amrubicinol in PC-6/AMR-OH cells was decreased to about 15 percent of that in PC-6 cells. Treatment with verapamil and siRNA against MDR1 significantly increased the sensitivity to amrubicinol in PC-6/AMR-OH cells with increased cellular accumulation of amrubicinol. Meanwhile, neither MDR1 gene expression levels nor SNPs of the gene were associated with amrubicinol sensitivity. CONCLUSIONS: Results of this study indicate that increased MDR1 expression and P-gp activity confer acquired resistance to amrubicinol. In contrast, neither expression level nor SNPs of MDR1 are likely to be predictive markers for amrubicin activity.

Amrubicin monotherapy for elderly patients with previously treated lung cancer.

OBJECTIVE: The novel anthracycline agent amrubicin, has been approved in Japan to treat small and non-small cell lung cancers (SCLC and NSCLC). The present study evaluates the toxicity and effect of amrubicin especially in elderly patients with previously treated lung cancer. PATIENTS AND METHODS: This retrospective study analyzed data from 51 patients (<70 years of age, n=29; > oor =70 years of age, n=22) with lung cancer (NSCLC, n=21; SCLC, n=30) who were treated with amrubicin at our hospital, between July 2003 and October 2009. All patients had recurrent or refractory lung cancer after one or more chemotherapy regimens. We compared the outcomes of patients younger and older than 70 years of age. Amrubicin (30-40 mg/m(2)/day) was infused depending on patient performance status and laboratory data over a period of 5 minutes on days 1-3, with courses repeated at intervals of at least 3 weeks. The dose was modified according to myelosuppression. RESULTS: The mean number of treatment cycles, mean dose and mean interval of amrubicin administration did not significantly differ between patients aged <70 and > or =70 years. The rate of hematological toxicities (> or = Grade 3) also did not significantly differ between the two age groups (leukopenia, 48.3% and 59.1% for age <70 and > or =70 years, p=0.573; neutropenia, 65.5% vs. 77.3%, p=0.536; anemia, 20.7% vs. 22.7%, p=1.000; thrombocytopenia, 13.8% vs. 31.8%, p=0.173). The incidence of grade 2-4 non-hematological toxicities also did not significantly differ between the groups. The response rate of SCLC and disease control rate of NSCLC were similar in the younger and older groups. CONCLUSION: Amrubicin monotherapy might be equally tolerated by elderly and younger patients. Further studies are needed to investigate the benefit of amrubicin monotherapy among elderly patients with previously treated lung cancer.

ABCC11/MRP8 confers pemetrexed resistance in lung cancer.

We have previously shown that overexpression of thymidylate synthetase (TS) resulted in pemetrexed (MTA) resistance. To investigate another mechanism of MTA resistance, we investigated the expression of ATP-binding cassette (ABC)-transporters in MTA-resistant lung cancer cell lines and found that the gene and protein expression of ABCC11/MRP8 (ABCC11) was higher in MTA-resistant cells than in the parental cells. The MTA resistant cells showed cross-resistance to methotrexate (MTX), which is a substrate for ABCC11, and intracellular MTX accumulation in MTA-resistant cells was lower than in the parental cells. We then tested the effect of decreasing the expression of ABCC11 by siRNA and found that decreased expression of ABCC11 enhanced MTA cytotoxicity and increased intracellular MTX accumulation in MTA-resistant cells. These findings suggested that ABCC11 directly confers resistance to MTA by enhancing efflux of the intracellular anti-cancer drug. Next, we analyzed the relationship between ABCC11 gene expression and MTA sensitivity of 13 adenocarcinoma cells, but there was no correlation. The ABCC11 gene has been shown to have a functional single-nucleotide polymorphism (SNP), 538G>A. We then classified 13 lung adenocarcinoma cell lines into three groups based on the genotype of this ABCC11 SNP: G/G, G/A and A/A. The A/A group showed a significant reduction in the IC(50) of MTA compared with the combined G/G and G/A groups, indicating that the SNP (538G>A) in the ABCC11 gene is an important determinant of MTA sensitivity. These results showed that ABCC11 may be one of the biomarkers for MTA treatment in adenocarcinomas.

Significance of thymidylate synthase for resistance to pemetrexed in lung cancer.

Pemetrexed (MTA) is a multitargeted antifolate with promising clinical activity in lung cancer. We exposed the small cell lung cancer cell line PC6 to stepwise-increasing pemetrexed concentrations of 0.4, 1.6, and 4.0 microm, and established three pemetrexed-resistant lung cancer cell lines: PC6/MTA-0.4, PC6/MTA-1.6, and PC6/MTA-4.0 cells. To investigate the mechanisms of acquired resistance to pemetrexed, we measured the expression levels of the thymidylate synthase (TS), reduced folate carrier (RFC), and folylpoly-gamma-glutamate synthetase (FPGS) genes. TS gene expression was significantly increased in PC6/MTA-1.6 and PC6/MTA-4.0 cells relative to parental cells in a pemetrexed dose-dependent manner. In contrast, the levels of RFC gene expression in PC6/MTA-0.4 cells and FPGS in PC6/MTA-1.6 cells were significantly decreased, whereas the levels of both genes were restored in PC6/MTA-4.0 cells. Knockdown of TS expression using siRNA enhanced pemetrexed cytotoxicity in PC6/MTA-4.0 cells. The expression level of the TS gene was significantly correlated with the concentration of pemetrexed for 50% cell survival (IC(50)) in 11 non-small cell lung cancer cell lines. These results suggest that the alteration of molecular pharmacological factors in relation with pemetrexed resistance is dose-dependent, and that up-regulation of the expression of the TS gene may have an important role in the acquired resistance to pemetrexed. In addition, TS may be a predictive marker for pemetrexed sensitivity in lung cancer.

Efficacy of S-1 monotherapy for non-small cell lung cancer after the failure of two or more prior chemotherapy regimens.

The efficacy and safety of S-1 monotherapy for patients with advanced or recurrent non-small cell lung cancer (NSCLC) after the failure of two or more prior chemotherapy regimens were investigated. Records of 36 patients with advanced or recurrent NSCLC who received S-1 monotherapy between January 2005 and December 2008, following the failure of previous chemotherapy, were reviewed retrospectively at two institutions. S-1 was given orally twice daily on days 1-28 every six weeks; the dose was based on body surface area. The median number of prior chemotherapy regimens was three (range 2-5), and that of courses given per patient was two (range 1-10). No patient achieved complete response, 4 patients (11.1%) achieved partial response, 10 patients (27%) had stable disease and 18 patients (50%) had progressive disease. The median progression-free survival was 3 months and the median overall survival was 15.2 months. No grade 4 hematological toxicity was noted. Grade ≥3 non-hematological toxicities were observed in 5 patients (13.9%). No deaths related to S-1 monotherapy occurred. S-1 monotherapy exhibits activity with acceptable toxicity as third-line or subsequent chemotherapy for advanced NSCLC.

[Two cases of recurrent non-small cell lung cancer successfully treated with S-1 as fifth-line chemotherapy].

There is at present no defined role for S-1 chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) who previously failed chemotherapy. Two cases of multidrug-resistant, NSCLC that were successfully treated with S-1 as fifth-line chemotherapy are reported. A 75-year-old man was diagnosed as having pulmonary adenocarcinoma, cT1N3M0, stage III B. He was treated with S-1 as fifth-line chemotherapy after treatment with cisplatin(CDDP)and vinorelbine(VNR), docetaxel (DOC), gemcitabine (GEM) and VNR, and amrubicin (AMR). After completing two courses, chest computed tomography(CT)showed a partial response( PR)of the recurrent tumors, and the serum carcinoembryonic antigen level decreased. Currently, seven courses have been completed, and this treatment will be continued due to the tumor response of stable disease. A 65-year-old woman was referred for treatment of recurrent pulmonary adenocarcinoma after right upper lobe resection. She was treated with S-1 as fifth-line chemotherapy after treatment with GEM and VNR, carboplatin(CBDCA) and paclitaxel ( PTX), DOC, and gefitinib. After completing five courses, chest CT showed PR of the intrapulmonary metastases. Though grade 3 toxicity-anemia in the first case and an elevated serum amylase level in the second case were observed in both cases, the patients' quality of life was preserved. S-1 could therefore be a treatment option for patients with advanced NSCLC who previously underwent chemotherapy unsuccessfully.

Small-cell lung cancer arising after chemotherapy for a patient with lymphoma of pulmonary mucosa-associated lymphoid tissue-a case report.

A 76-year-old woman was admitted to our hospital with infiltrations evident in the right lower lobe on chest computed tomography. Bronchoscopic biopsy showed lymphoma of mucosa-associated lymphoid tissue (MALT). Lymphoma of the pulmonary MALT became enlarged at 8 months after diagnosis and dyspnea developed. Four courses of chemotherapy(rituximab+ cladribine)resulted in a partial response. However, 14 months after the chemotherapy, she developed multiple lung and liver tumors accompanied by disseminated intravascular coagulation syndrome. A histological examination of bone marrow aspiration showed small cell carcinoma. We administered one course of carboplatin and etoposide, but bone marrow suppression was so severe that further chemotherapy was precluded. To our knowledge, this is a rare case of small cell lung cancer arising from the treatment of lymphoma of pulmonary MALT.