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Introduction Combined treatment using anti-programmed death-ligand 1 antibody (anti-PD-L1) and platinum-etoposide is the current standard first-line treatment for patients with extensive-stage (ES) small cell lung cancer (SCLC). However, the best treatment for relapsed ES-SCLC after the first-line treatment remains unclear. There are some approved chemotherapeutic agents that can be used against ES-SCLC, and treatment with irinotecan is well established as both, a monotherapy and a combined therapy, in combination with platinum. Therefore, we conduct a phase II study with irinotecan in the second- or later-line setting for patients with ES-SCLC who are previously treated with a combination of anti-PD-L1 and platinum-etoposide. Methods Our study will enroll patients who are diagnosed with ES-SCLC and experienced disease progression after treatment of anti-PD-L1 and platinum-etoposide. Patients will receive irinotecan on days 1, 8, and 15, which will be repeated every 4 weeks. Doses of irinotecan (100/80/60 mg/m2) will be determined according to the type of UGT1A1 gene polymorphism, and the treatment will be discontinued following disease progression, intolerance, withdrawal of patient consent, and based on the investigator’s decision. The primary endpoint of the study is the response rate, and the secondary endpoints are overall survival, progression-free survival, and safety. Discussion Since the present first-line treatment has been changed to combined treatment with anti-PD-L1 and platinum-etoposide, the second- or later-line treatment should be re-evaluated for patients with relapsed SCLC. Irinotecan is a major chemotherapeutic agent used for SCLC. This IRICO study demonstrates and re-evaluates the clinical benefits of irinotecan after combined treatment with anti-PD-L1 and platinum-etoposide for patients with ES-SCLC. Registration details This study was registered in the Japan Registry of Clinical Trials (no. jRCT s071210090) on November 4, 2021.

Etoposide plus cisplatin (EP) combined with concurrent accelerated hyperfractionated thoracic radiotherapy (AHTRT) is the standard treatment strategy for unresectable limited-disease (LD) small cell lung cancer (SCLC), which has remained unchanged for over two decades. Based on a previous study that confirmed the non-inferiority of amrubicin (AMR) plus cisplatin (AP) when compared with EP for extensive-disease (ED) SCLC, we have previously conducted a phase I study assessing AP with concurrent TRT (2 Gy/time, once daily, 50 Gy in total) for LD-SCLC therapy. Our findings revealed that AP with concurrent TRT could prolong overall survival to 39.5 months with manageable toxicities. Therefore, we plan to conduct a phase I study to investigate and determine the effect of AP combined with AHTRT, recommended dose (RD), maximum tolerated dose (MTD), and dose-limiting toxicity (DLT) of AP in patients with LD-SCLC.Treatment-naive patients with LD-SCLC, age between 20 and 75 years, who had a performance status of 0 or 1 and adequate organ functions will be enrolled. For chemotherapy, cisplatin 60 mg/mBased on our previous study, the initial dose of AMR 25 mg/m

Background Osimertinib is one of the standard first-line treatments for advanced non-small cell lung cancer in patients with epidermal growth factor receptor (EGFR) mutations, because it achieves significantly longer progression-free survival (PFS) than conventional first-line treatments (hazard ratio: 0.46). However, the efficacy and safety of osimertinib as a first-line treatment for patients aged ≥75 years remain unclear. Methods This phase II study was performed to prospectively investigate the efficacy and safety of osimertinib for elderly patients with EGFR mutation-positive advanced non-small cell lung cancer. The primary endpoint was 1-year PFS rate; secondary endpoints were overall response rate (ORR), PFS, overall survival (OS), and safety. Results Thirty-eight patients were included in the analysis. The 1-year PFS rate was 59.4% (95% confidence interval [CI], 46.1%-72.7%), which did not meet the primary endpoint (the threshold 1-year PFS rate of 50% predicted using data from the NEJ003 study). The most common grade 3/4 adverse events were rash/dermatitis acneiform/ALT increased/hypokalemia (2 patients, 5%). Seven patients developed pneumonitis (17.5%). There were no other cases of treatment discontinuation due to adverse events other than pneumonitis. Conclusion Although this study did not meet the primary endpoint, osimertinib was tolerable for elderly patients with EGFR mutation-positive advanced non-small cell lung cancer. (Japan Registry of Clinical Trials [JRCT] ID number: jRCTs071180007).

A 78-year-old man was admitted to our hospital for multiple lung and liver tumors. Initial clinical diagnosis was hepatocellular carcinoma (HCC) with lung metastases because of a high value of serum protein induced by vitamin K absence or antagonist II (PIVKA-II) (6,705 mAU/mL). However, a review of a prior CT showed the lung tumor had existed 6 months before liver tumors were detected. The tumors progressed rapidly and the patient died 37 days after admission. Autopsy revealed that both lung and liver tumors exhibited the histology of large cell neuroendocrine carcinoma (LCNEC). Immunohistochemistry revealed that the tumor cells expressed not only neuroendocrine markers but also PIVKA-II diffusely. Hepatoid differentiation was not detected. Background liver did not show any chronic liver disease. The final diagnosis was PIVKA-II producing LCNEC of the lung with multiple liver metastases. PIVKA-II producing tumors other than HCC are extremely rare. To our best knowledge, this is the first case report of PIVKA-II producing neuroendocrine tumors of the lung.

Amrubicin and cisplatin is one of the active regimens used to treat patients with extensive-disease (ED)-small cell lung cancer (SCLC), whereas combined therapy involving chemotherapy and concurrent thoracic radiotherapy is the standard treatment for limited-disease (LD)-SCLC. This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of amrubicin and cisplatin with concurrent thoracic radiotherapy (TRT) for LD-SCLC. Patients that fulfilled the following eligibility criteria were enrolled: being aged ≤ 75 years and chemotherapy-naive and having a performance status (PS) of 0–1, LD-SCLC, and adequate organ function. The patients received escalating doses of amrubicin on days 1, 2, and 3, and a fixed 60-mg/m2 dose of cisplatin on day 1. Four cycles of chemotherapy were administered, with each cycle lasting 4 weeks. TRT involving 2 Gy/day, once daily, commenced on day 2 of the first cycle of chemotherapy. The initial dose of amrubicin was 20 mg/m2 (level 1), and the dose was escalated to 25 mg/m2 (level 2) and then 30 mg/m2 (level 3). Eight patients from three institutions were enrolled at three dose levels. The patients’ characteristics were as follows: male/female: 3/5; median age (range): 68.5 (60–73); PS 0/1: 4/4; stage IIIA/IIIB disease: 3/5. Both level 3 patients experienced DLT (grade 4 neutropenia and/or leukopenia lasting > 4 days). Level 3 was defined as the MTD, and level 2 was recommended as the dose for this regimen. Seven patients exhibited partial responses, and 1 displayed progressive disease (response rate: 88%). The median progression-free survival and overall survival periods were 11.1 and 39.5 months, respectively. No treatment-related deaths occurred. When this regimen was combined with TRT for LD-SCLC, the MTD was 30 mg/m2 for amrubicin and 60 mg/m2 for cisplatin. In addition, neutropenia and leukopenia were DLT, and doses of 25 mg/m2 for amrubicin and 60 mg/m2 for cisplatin are recommended for this regimen.

Background Various polymorphisms have been detected in the UDP-glucuronosyltransferase 1A ( UGT1A ) gene, and UGT1A1 *28 and UGT1A1 *6 have important effects on the pharmacokinetics of irinotecan and the risk of severe toxicities during irinotecan therapy. This study was conducted to determine the maximum tolerated dose (MTD) of irinotecan chemotherapy according to the UGT1A1 genotype in previously treated lung cancer patients with the UGT1A1 *28 or UGT1A1 *6 polymorphism. Methods The eligibility criteria were as follows: lung cancer patients that had previously been treated with anticancer agents other than irinotecan, possessed the UGT1A1 *28 or UGT1A1 *6 polymorphism (group A included *28/*28, *6/*6, and *28/*6, and group B included *28 /− and *6 /−), were aged ≤75 years old, had a performance score of 0–1, and exhibited adequate bone marrow function. The patients were scheduled to receive irinotecan on days 1, 8, 15, 22, 29, and 36. Results Four patients were enrolled in this trial. Two patients were determined to be ineligible. The remaining two patients, who belonged to group B, received an initial irinotecan dose of 60 mg/m2, but did not complete the planned treatment because of diarrhea and leukopenia. Thus, in group B patients, 60 mg/m2 was considered to be the MTD of irinotecan. The study was terminated in group A because of poor case recruitment. Conclusions The MTD of irinotecan for previously treated lung cancer patients that are heterozygous for the UGT1A1 * 28 or UGT1A1 * 6 gene polymorphism is 60 mg/m2.

We herein report the first case of pulmonary metastasis with lepidic growth that originated from cholangiocarcinoma. A 77-year-old man was admitted to our hospital due to exertional dyspnea and liver dysfunction. Computed tomography showed widespread infiltration and a ground-glass opacity in the lung and dilation of the intrahepatic bile duct. The pulmonary lesion progressed rapidly, and the patient died of respiratory failure. Cholangiocarcinoma and lepidic pulmonary metastasis were pathologically diagnosed by an autopsy. Lepidic pulmonary growth is an atypical pattern of metastasis, and immunopathological staining is useful to distinguish pulmonary metastasis from extrapulmonary cancer and primary pulmonary adenocarcinoma., Internal Medicine, 55(19), pp.2849-2853; 2016

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used for treating EGFR-mutated lung cancer, and osimertinib is effective in cases that acquired T790M mutations after treatment with the first- and second-generation EGFR-TKIs. However, no study has evaluated its safety and efficacy in older patients. This phase II trial (jRCTs071180002) evaluated osimertinib in T790M mutation-positive Japanese patients who were &ge, 75 years old and had experienced relapse or progression after previous EGFR-TKI treatment. Our previous report that enrolled 36 patients showed the overall response rate (58.3%) and disease control rate (97.2%), while this report describes the results for the progression-free survival (PFS), overall survival (OS), and safety analyses. The median PFS was 11.9 months (95% confidence interval (CI): 7.9&ndash, 17.5), and the median OS was 22.0 months (95% CI: 16.0 months&ndash, not reached). The most frequent adverse events were anemia/hypoalbuminemia (27 patients, 75.0%), thrombocytopenia (21 patients, 58.3%), and paronychia/anorexia/diarrhea/neutropenia (15 patients, 41.7%). Pneumonitis was observed in four patients (11.1%), including two patients (5.6%) with Grade 3&ndash, 4 pneumonitis. These results suggest that osimertinib was relatively safe and effective for non-small cell lung cancer that acquired T790M mutations after previous EGFR-TKI treatment, even among patients who were &ge, 75 years old.

Background: S-1, a novel oral fluoropyrimidine, is active in the treatment of non-small cell lung cancer (NSCLC). However, data on S-1 for elderly patients with NSCLC are insufficient. Methods: Eligibility criteria were no prior chemotherapy, stage IIIB or IV NSCLC, performance status 0-1, age >70 years, and adequate hematological, hepatic, and renal functions. Patients received S-1 (40 mg/m2 twice a day) for 28 consecutive days. This schedule was repeated every 6 weeks. The primary end point was the tumor response rate. Results: Thirty-two patients were enrolled and 31 patients were evaluable for response. The patients' median age was 80 years (range: 71-88). The response rate was 22.6% (95% CI: 11-38). Neutropenia, anemia, thrombocytopenia, febrile neutropenia, and diarrhea of grade ≥3 occurred in 6, 6, 10, 3, and 3%, respectively. Conclusions: In elderly patients with previously untreated advanced NSCLC, S-1 appears to be well tolerated and demonstrates encouraging activity.

It is widely recognized that the risk of secondary neoplasms increases as childhood cancer survivors progress through adulthood. These are mainly hematological malignancies, and recurrent chromosome translocations are commonly detected in such cases. On the other hand, while secondary epithelial malignancies have sometimes been reported, chromosome translocations in these epithelial malignancies have not. A 33-year-old man who had been diagnosed with acute lymphoblastic leukemia and treated with chemotherapy almost 20 years earlier was diagnosed with lung adenocarcinoma. After chromosomal rearrangement of echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene was detected in this adenocarcinoma, he responded to treatment with crizotinib. It was therefore concluded that this echinoderm microtubule-associated protein-like 4 gene-anaplastic lymphoma kinase gene-positive lung adenocarcinoma was a secondary epithelial malignancy.

Lessons Learned Non-small-cell lung cancer (NSCLC) represents 85% of lung cancer in elderly patients. In the present study performed in the 36 elderly subjects with epidermal growth factor receptor (EGFR) T790M mutation-positive NSCLC, osimertinib 80 mg demonstrated statistically significant improvement in the objective response rate, which was comparable to those in the nonelderly population. Osimertinib appears to be an effective and safe treatment option in elderly patients with advanced NSCLC with EGFR mutation; further research in larger scale is warranted. Background Previous findings suggest the possibility of relatively safe use of osimertinib for patients with T790M-positive non-small-cell lung cancer (NSCLC), with few serious adverse events for the elderly in comparison with conventional endothelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), and with an antitumor effect. Methods This phase II study was performed to prospectively investigate the efficacy and safety of osimertinib for elderly patients aged ≥75 years with ineffective prior EGFR TKI treatment or with recurrence in T790M EGFR TKI resistance mutation-positive NSCLC. Results A total of 36 patients were included in the analyses. Among the 36 subjects, 63.9% were female, with mean age of 79.9 years. The objective response rate (ORR) was 58.3% (95% confidence interval [CI], 42.2%–72.9%), demonstrating statistically significant efficacy of osimertinib (p = .0017). The median duration of response (DOR) was 27.9 weeks (95% CI, 21.1–82.0). Complete response (CR) and partial response (PR) were 2.8% and 55.6%, respectively. Disease control rate (DCR) was 97.2%. A waterfall plot revealed that 33 (91.6%) subjects exhibited tumor shrinkage during treatment, including 12 of 14 subjects who had stable disease (SD). All adverse events were not reason for discontinuation of the study drug. Conclusion Osimertinib may be an effective and safe treatment option in elderly patients with advanced NSCLC with EGFR mutation.

A 65-year-old man was admitted to our hospital with a temperature of 39.3 C, cough, sputum, and pharyngeal discomfort that had persisted for 3 days. He had been treated with methotrexate and adalimumab (a tumor necrosis factor-alpha [TNF-α] inhibitor) for rheumatoid arthritis for 2 years, and he had also been treated with S-1 (tegafur, gimeracil, and oteracil potassium) for pancreatic metastasis of gastric cancer for 2 months. Regardless of the underlying pathologies, his general condition was good and he had worked as an electrician until 2 days before admission. However, his appetite had suddenly decreased from the day before admission, and high fever and hypoxia were also evident upon admission. A chest X-ray and computed tomography scan revealed left pleural effusion and consolidation in both lungs. The pneumonia severity index score was 165 and the risk class was V. Accordingly, we started to treat the pneumonia with a combination of levofloxacin and meropenem. Thereafter, we received positive urinary antigen test findings for Legionella pneumophila. After hospitalization, hypoxia was progressed and hypotension was emerged. Despite the application of appropriate antibiotics, vasopressors, and oxygenation, the patient died 8 h after admission. Even after his death, blood cultures were continued to consider the possibility of bacterial co-infection. Although no bacteria were detected from blood cultures, Gimenez staining revealed pink bacteria in blood culture fluids. Subsequent blood fluid culture in selective medium revealed L. pneumophila serogroup 1. Recently, TNF-α inhibitors have been described as a risk factor for Legionnaires' disease. In consideration of the increased frequency of TNF-α inhibitors, we may need to recognize anew that L. pneumophila might be a pathogen of severe community-acquired pneumonia., Journal of Infection and Chemotherapy, 19(1), pp.166-170; 2013

Background. Superior vena cava syndrome (SVCS is a serious complication of cancer; however intravenous stenting is infrequently performed as treatment for SVCS in Japan because the procedure has not been approved for coverage by the Japanese national health insurance program. Case Report. A 67‑year‑old male undergoing chemotherapy for malignant pleural mesothelioma developed dyspnea and was admitted to our hos‑ pital two years and two months after receiving the cancer diagnosis. On CT the patients right pleural lesion ex‑ hibited enlargement causing stenosis of the SVC right main pulmonary artery and right main bronchus. He pre‑ sented with edema of the upper body including the face and cervical vein swelling and SVCS was diagnosed. The dyspnea increased in severity in spite of a well‑maintained SpO2 value and the patient developed an urgent status; therefore it became difficult to wait for the effects of radiotherapy. After obtaining informed consent from the patient and his family SVC stenting was performed. The patients symptoms immediately improved following treatment and no complications were observed. The SVCS did not recur for three months after which the pa‑ tient moved into home medical care. Conclusion. Our results in this case show that SVC stenting is a useful thera‑ peutic option for treating SVCS caused by malignant mesotheliomas. Furthermore we expect that endovascular treatment for SVCS will be approved for coverage under the Japanese national health insurance program. (JJLC. 2013;53:250‑254

Background As the toxicity associated with the α-GalCer-pulsed dendritic cell (DC) therapy could be considered to be negligible, its addition to postoperative adjuvant chemotherapy would be expected to greatly improve the therapeutic effect, and could result in prolonged survival. The aim of the present study is to compare the therapeutic efficacy of alpha-galactosylceramide-pulsed DC therapy in patients who have undergone a complete resection of stage II–IIIA non-small-cell lung cancer (NSCLC) followed by postoperative adjuvant therapy with cisplatin plus vinorelbine, to that in patients who did not receive additional treatment (surgical resection plus postoperative adjuvant chemotherapy only). Methods Subsequent to the complete resection of NSCLC, followed by the administration of cisplatin plus vinorelbine dual-agent combination adjuvant chemotherapy, patients who satisfy the inclusion criteria will be randomly allocated to either the α-GalCer-pulsed DC immune therapy group, or the standard treatment group. In total, 56 patients will be included in the study. The primary endpoint is recurrence-free survival, and the secondary endpoints are natural killer T-cell-specific immune response, the frequency of toxic effects and safety, and overall survival. Discussion In order to determine the efficacy of α-GalCer-pulsed DC therapy, the present study compares patients with stage II–III NSCLC who underwent complete surgical resection followed by postoperative adjuvant therapy with cisplatin plus vinorelbine, to those who did not receive additional treatment (surgical resection plus postoperative adjuvant chemotherapy only). Trial registration UMIN000010386 (R000012145). Registered on 1 April 2013. UMIN-CTR is officially recognized as a registration site which satisfies ICMJE criteria. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2103-4) contains supplementary material, which is available to authorized users.

A 78-year-old man was admitted to our hospital for multiple lung and liver tumors. Initial clinical diagnosis was hepatocellular carcinoma (HCC) with lung metastases because of a high value of serum protein induced by vitamin K absence or antagonist II (PIVKA-II) (6,705 mAU/mL). However, a review of a prior CT showed the lung tumor had existed 6 months before liver tumors were detected. The tumors progressed rapidly and the patient died 37 days after admission. Autopsy revealed that both lung and liver tumors exhibited the histology of large cell neuroendocrine carcinoma (LCNEC). Immunohistochemistry revealed that the tumor cells expressed not only neuroendocrine markers but also PIVKA-II diffusely. Hepatoid differentiation was not detected. Background liver did not show any chronic liver disease. The final diagnosis was PIVKA-II producing LCNEC of the lung with multiple liver metastases. PIVKA-II producing tumors other than HCC are extremely rare. To our best knowledge, this is the first case report of PIVKA-II producing neuroendocrine tumors of the lung.

We consider the problem of online automatic tuning. In this setting, we execute the target program with some tuning parameters N times, where N is given, while optimizing the parameters to minimize some objective function such as the total execution time. Thus we have to choose the parameters for each execution by taking into account the trade-off between exploration and exploitation. The ATMathCoreLib library developed by Suda is a set of software that solves this problem. To model the performance of the target software, ATMathCoreLib uses a linear statistical model, and its basis functions must be provided by the user. In this paper, we investigate how to choose the basis functions appropriately, using the singular value decomposition of a square matrix as an example. We consider three cases, namely, (I) when the performance characteristics of the target problem are well understood by the user, (II) when the tuning parameter has a complicated structure, as occurs in the case of simultaneous selection of an algorithm and its parameter, and (III) when the performance characteristics of the target problem are not known to the user. The results of using ATMathCoreLib with different basis functions for each case are given. They help one understand the tuning by ATMathCoreLib and contribute to the progress of ATMathCoreLib.

Background Various polymorphisms have been detected in the UDP‐glucuronosyltransferase 1A (UGT1A) gene, and UGT1A1 *28 and UGT1A1 *6 have important effects on the pharmacokinetics of irinotecan and the risk of severe toxicities during irinotecan therapy. This study was conducted to determine the maximum tolerated dose (MTD) of irinotecan chemotherapy according to the UGT1A1 genotype in previously treated lung cancer patients with the UGT1A1 *28 or UGT1A1 *6 polymorphism. Methods The eligibility criteria were as follows: lung cancer patients that had previously been treated with anticancer agents other than irinotecan, possessed the UGT1A1 *28 or UGT1A1 *6 polymorphism (group A included *28/*28, *6/*6, and *28/*6, and group B included *28 /− and *6 /−), were aged ≤75 years old, had a performance score of 0–1, and exhibited adequate bone marrow function. The patients were scheduled to receive irinotecan on days 1, 8, 15, 22, 29, and 36. Results Four patients were enrolled in this trial. Two patients were determined to be ineligible. The remaining two patients, who belonged to group B, received an initial irinotecan dose of 60 mg/m2, but did not complete the planned treatment because of diarrhea and leukopenia. Thus, in group B patients, 60 mg/m2 was considered to be the MTD of irinotecan. The study was terminated in group A because of poor case recruitment. Conclusions The MTD of irinotecan for previously treated lung cancer patients that are heterozygous for the UGT1A1 * 28 or UGT1A1 * 6 gene polymorphism is 60 mg/m2.

The safety and efficacy of platinum-based combination chemotherapy for elderly patients with advanced Non-Small-cell lung cancer (NSCLC) remains unclear. We conducted phase I and phase II trials of a combination of vinorelbine and carboplatin for patients, Clinical Lung Cancer, 13(5), pp.347-351; 2012

BackgroundAmrubicin and cisplatin are active in the treatment of small cell lung cancer (SCLC), and carboplatin is an analogue of cisplatin with less nonhematological toxicity. The appropriate dose of amrubicin and carboplatin combination chemotherapy for previously untreated patients with extensive-disease (ED) SCLC has not been established.PurposeTo determine the maximum-tolerated dose and dose-limiting toxicity (DLT) of amrubicin and carboplatin in ED-SCLC.Patients and methodsEligibility criteria were chemotherapy-naive ED-SCLC patients, performance status 0–1, age ≤75, and adequate hematological, hepatic, and renal function. Patients received escalating amrubicin doses under a fixed target area under the curve (AUC) 5 of carboplatin (Chatelut formula). Amrubicin and carboplatin were administered by intravenous (IV) infusion on days 1, 2, and 3, and day 1, respectively. The initial dose of amrubicin was 30 mg/m2, and the dose was escalated to 35 and 40 mg/m2.ResultsSixteen patients were enrolled and 15 eligible patients were evaluated. One of six patients in level 1, one of six in level 2, and three of three in level 3 experienced DLTs. The presentation of DLTs included neutropenia, leukopenia, thrombocytopenia, febrile neutropenia, and liver dysfunction. Evaluation of responses were two complete response, nine partial response, three stable disease, and one progressive disease (response rate 73%), and the median survival time was 13.6 months. The maximum-tolerated doses of amrubicin and carboplatin were determined as 40 mg/m2 and AUC 5. A dose of 35 mg/m2 amrubicin and carboplatin AUC 5 was recommended in this regimen.ConclusionsThis regimen is associated with an acceptable tolerability profile, and warrants evaluation in the phase II setting.

PURPOSE The treatment strategy for patients with non–small-cell lung cancer (NSCLC) involving ipsilateral mediastinal lymph nodes is still controversial. We performed a phase II feasibility study of induction chemotherapy followed by surgery for patients with pathologic N2 NSCLC. PATIENTS AND METHODS Patients with mediastinoscopy- positive stage IIIA N2 NSCLC received 2 cycles of cisplatin 80 mg/m2, vinorelbine 25 mg/m2, and mitomycin-C 8 mg/m2. Patients without progressive disease underwent thoracotomy and lobectomy with lymph node dissections 2-4 weeks later. RESULTS From January 2000 to July 2004, 24 eligible patients (15 men, 9 women) were enrolled. Induction chemotherapy was completed as planned in 23 patients (95.8%). Hematological toxicity was the primary grade 3/4 toxicity. Twelve (50%) patients achieved a partial response. Twenty-three patients underwent surgical resection, and complete resection was achieved in 22 patients (95.7%). There were no surgery-related deaths. Pathologic complete response in metastatic lymph nodes was achieved in 5 patients. With a median follow-up of 5.4 years (range, 2.88-7.7 years), the estimated 5-year survival was 51.8% (95% CI, 41.3-62.3) and progression-free survival was 46.6% (95% CI, 36–57.2). CONCLUSION Induction chemotherapy followed by surgery for patients with pathologic N2 NSCLC was feasible and associated with high response to lymph node metastasis and good survival.

Purpose: Breast cancer resistance protein (BCRP) confers resistance against topoisomerase I inhibitors in cancer cells. Very recently, we reported that gefitinib reverses BCRP-mediated drug resistance by direct inhibition. However, it remains undetermined how much BCRP contributes to the resistance to topoisomerase I inhibitors in non-small cell lung cancer (NSCLC). The present study was designed to examine whether BCRP levels in NSCLC cells are correlated with the resistance to topoisomerase I inhibitors and the reversal effect by gefitinib. Methods: BCRP levels and its function were evaluated by Western blotting and flowcytometry, respectively. Gefitinib-insensitive NSCLC cells expressed various levels of BCRP, which were closely correlated not only with the IC50 values of SN-38 (r=0.874, P

Purpose: The combination of carboplatin and etoposide is currently considered the most appropriate regimen for treating elderly patients with small-cell lung cancer (SCLC). Previous reports on elderly patients, 70 years or older, found that the recommended dose was close to that of younger patients. Then, we conducted a phase I study of carboplatin and etoposide in elderly patients, 75 years or older, with SCLC. This study aimed to determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT). Methods: Twenty-six patients fulfilling the eligibility criteria, chemotherapy-naive, performance status (PS) of 0–2, age ≥75, and adequate organ functions were enrolled. Patients’ characteristics were: male/female=21/5; PS 0/1/2=9/11/6; median age (range)=78 (75–82); and limited/extensive stage=16/10. The patients intravenously received carboplatin with a target AUC of 4 or 5 mg min/ml (Chatelut formula) on day 1 and etoposide at 80–120 mg/m2 on days 1, 2 and 3. Therapy was repeated four times in every 4 weeks. Results: The MTD of carboplatin/etoposide was AUC=5/80, 4/110, and 4/120. The DLTs were thrombocytopenia, neutropenia, leukopenia, and febrile neutropenia. Overall, grade 4 thrombocytopenia, neutropenia (≥4 days), leukopenia (≥4 days), and febrile neutropenia occurred in 27, 20, 7, and 13% of cases at MTD levels, respectively, and 0% at other levels. Twenty of 26 patients showed objective responses (2CR, 18PR; RR=77%). Conclusion: A dose of carboplatin of AUC=4 and etoposide of 100 mg/m2 was recommended in this regimen.

We encountered a rare case of the left common iliac artery in a 92-year-old Japanese female cadaver during dissection practice for medical students. The artery entered into the small pelvis without branching to the external iliac artery. There, it went down slightly medially and then turned laterally and passed behind the first sacral nerve. The artery ran anterolaterally further and returned to the greater pelvis and became the external iliac artery, which continued to the femoral artery as usual. During the course in the small pelvis, the artery branched to give rise to each branch of the internal iliac artery. We speculate that in the present case, a communication between the median sacral artery and the superior gluteal artery, passing behind the first sacral nerve, enlarged and compensated the usual common iliac artery.

An anomalous muscle was found in the superficial region of the right popliteal fossa in a 90-year-old Japanese female cadaver during dissection practice for medical students. The muscle ran transversely between the medial head of the gastrocnemius muscle and the tendon of the biceps femoris muscle, covering the nerves, vessels and muscle in the popliteal fossa. The muscle received its nerve supply from the common peroneal nerve. Based on the result of nerve fiber analysis, we speculated that the anomalous muscle might be close to the short head of the biceps femoris muscle in its derivation.

Irinotecan, a topoisomerase I inhibitor, is an effective agent for non-small-cell lung cancer (NSCLC). To determine the efficacy and toxicity of irinotecan and carboplatin, we conducted a phase II study in 61 patients with advanced NSCLC. Every 4 weeks, the patients received irinotecan 50 mg/m2 (days 1, 8 and 15) and carboplatin (day 1) with a target AUC of 5 mg min/ml using the Chatelut formula. All patients were evaluable for toxicity, and of 59 patients evaluable for response, 20 achieved a partial response and 26 showed no change. The overall response rate was 34% (95% confidence interval 23–48%). Grade 3 or 4 anemia, leukopenia, neutropenia, thrombocytopenia and diarrhea occurred in 32%, 32%, 60%, 25%, and 7%, respectively. The median survival time and 1-year, and 2-year survival rates were 10.0 months, 37.6%, and 15.2%, respectively. Irinotecan with carboplatin is effective for advanced NSCLC and safe.

A phase I/II study of combination chemotherapy with amrubicin and nedaplatin for patients with untreated, advanced, non-small cell lung cancer (NSCLC) was conducted. Amrubicin was given on days 1-3, with nedaplatin given on day 1. The treatment was repeated every 3 weeks. In the phase I trial, the initial amrubicin dose of 25 mg/m2 was escalated in 5-mg/m2 increments until the maximum tolerated dose was reached, with the dose of nedaplatin fixed at 100 mg/m2. In the phase II trial, the primary endpoint was the overall response rate (ORR), assuming 20% for a standard therapy and 40% for a target therapy (α = 0.05 and β = 0.20), and the estimated required total number of patients was 35. In the phase I study, nedaplatin 100 mg/m2 and amrubicin 25 mg/m2 was recommended. In the phase II study, 17 out of 35 patients achieved a partial response, and the ORR was 48.6%. Grade 3/4 neutropenia, grade 3 anemia and grade 3/4 thrombocytopenia occurred in 62.9, 11.4 and 11.4% of cycles, respectively. Febrile neutropenia occurred in 5 cycles (3.9%) and all cases were manageable. The recommended dose of this combination is well tolerated and effective in patients with advanced NSCLC.

There has been no literature which reports a case of interstitial lung disease associated with sorafenib. However, a recent post-marketing survey in Japan revealed that interstitial pneumonia occurred in 4 among approximately 2 000 Japanese patients treated with sorafenib. In this article, we describe a Japanese patient with severe interstitial pneumonia probably caused by sorafenib treatment for metastatic renal cell carcinoma. Oncologists supervising future clinical trials for lung cancer should be alert to the fact that sorafenib can potentially induce serious interstitial lung disease, although this might depend on racial differences.

Incidence data of 22 cranial nonmetric traits were investigated in the Aeneolithic Yayoi people in the northwestern Kyushu area, and compared with those in Yayoi people in the northern Kyushu area, Yayoi people in Yamaguchi and Jomon people. Smith's Mean Measures of Divergence (MMD) were obtained in 8 groups after addition of modern people in the northwestern Kyushu area and others. Based on these data, principal co-ordinate analysis and cluster analysis were performed. The following results were obtained. The characteristics of the Yayoi people in northwestern Kyushu succeeded the characteristics of Neolithic Jomon people, and differ markedly from Yayoi people of continental lineage. Among the 22 traits, the incidences of supraorbital foramen, biasterionic suture vestige, hypoglossal canal bridging, pterygospinous foramen, transverse zygomatic suture vestige and mylohyoid bridging were greatly different between the Yayoi people in northwestern Kyushu and the Yayoi people of continental lineage. In the northwestern Kyushu area, a marked difference in cranial nonmetric traits was found between Yayoi and modern people. Such a difference probably developed because of the hereditary influence of Yayoi people of continental lineage in and after the Protohistoric Kofun period.

Objective: Our goal was to investigate whether the length and lead-time biases of radiologic screening for lung cancers vary according to the histologic type of the tumor. Methods: We analyzed the survival rates and radiographs of 119 cases of adenocarcinomas-large-cell carcinomas (ALC) and 50 peripheral squamous cell carcinomas (PSQ) detected in 205,401 screened individuals. Results: The sensitivity of screening and 5-year survival rates were 84.0% and 48.2% for ALC, and 52.0% and 18.5% for PSQ, respectively. The corrected length bias was 4.3% for ALC and 4.6% for PSQ. Stage III-IV ALC was often identified on 1-year-old films, but stage III-IV PSQ was not. Half of stage I ALC presented 2 or more years before detection, while half of stage I PSQ appeared within 1 year before detection. The survival rate of nonresected cases with stage I ALC was decreased 4 years after detection, while that of nonresected cases with stage I PSQ was decreased just after detection. The period of stage I ALC and PSQ was at least 6 years and 1 year, respectively. Conclusions: Slowly growing ALC had high sensitivity in radiologic screening and a high rate in 5-year survival, but had long lead time and delay in detection. PSQ grew rapidly resulting in low sensitivity in radiologic screening, and short lead time and survival. In both types, the magnitude of corrected length bias was not remarkable. The survival of ALC should be carefully evaluated because of the long lead time.

症例は81歳, 男性.咳, 労作時呼吸困難のため, 近医を受診し胸部X線で両下肺野の網状影および右肺門縦隔リンパ節腫張を指摘され当科に入院した.入院後, 右S9原発の進展型肺小細胞癌 (T4N2M0) と診断した.高齢で肺気腫を伴い, 腎機能もクレアチニンクリアランス31ml/分と低下が認められたが, Chatelut式を用いてAUC=5を目標とした第1日のカルボプラチンと第1-3日のエトポシド75mg/m2による併用化学療法を行った.第1コース目に測定したカルボプラチンのAUCは目標よりやや低い4.42であったが, 血液毒性はG-CSFの併用で耐用可能で4コースが施行され, 効果は70%縮小の有効であった.自覚的な副作用も軽く, 高齢・腎機能低下例においてもChatelut式を用いたこの治療法はG-CSFを併用すれば安全に施行可能なことが示唆された.

To assess the feasibility of treatments for patients with small cell lung cancer (SCLC) showing a poor performance status (PS, Eastern Cooperative Oncology Group; ECOG 3 or 4), we retrospectively reviewed the outcome for 13 SCLC patients showing poor PS treated at the National Cancer Center Hospital between January 1984 and May 1994. The main factors which contributed to poor prognosis were superior vena cava (SVC) syndrome, massive pleural effusion, tracheal stenosis due to lymph node swelling, pericardial effusion and pulmonary fibrosis (causing dyspnea in combination), brain metastasis resulting in neurological disturbance, cachexia, Eaton-Lambert syndrome causing muscle weakness, retroperitoneal lymph node metastasis causing abdominal pain, peritoneal effusion due to abdominal lymph node swelling, vertebral metastasis causing paraplegia, and dermatomyositis/polymyositis (DM/PM) causing muscle weakness. All of the patients received chemotherapy with or without radiotherapy. The PS of 8 patients improved with treatment, but no improvement was seen in 5. We analyzed these 13 patients and considered the treatments for those with poor PS. Chemo-radiotherapy was tolerable in SCLC patients showing PS 3, and improved their PS if severe conditions or combined disease did not arise concurrently. It was further suggested that PS 4 patients with severe conditions or combined disease should not be given the treatments.

To clarify the role of bronchoscopy for endotracheobronchial tuberculosis (EBTB), we performed a prospective study in 45 patients with active pulmonary tuberculosis, in 15 (33%) of whom bronchoscopic findings related to EBTB were seen. The findings were classified into six types: edematous hyperemic, submucosal nodule, ulcerative (shallowand deep), polypoid, cicatrical, and compression type. Each of these types was related to the healing process and outcome after antituberculosis chemotherapy. Serial bronchoscopy revealed that lesions less advanced than the deep ulcerative type responded to chemotherapy; the deep ulcerative and polypoid types progressed to cicatrical bronchostenosis despite chemotherapy. In the follow-up of patients with lesions of the deep ulcerative and polypoid types, serial bronchoscopy after chemotherapy is recommended; these patients also require adjunctive therapy to prevent cicatrical bronchostenosis.(Internal Medicine 35: 698-703, 1996)

Metrical dental characteristics were investigated in the Kofun series in southern Kyushu. The results of t-tests and Penrose's size distances showed that tooth size in the Kofun series in southern Kyushu was larger than those of the Jomon series and the Yayoi series in northwestern Kyushu, except for the buccolingual diameters in males of the Yayoi series, which were almost equal in size, although smaller than that of the Yayoi series in northern Kyushu. As regards Penrose's shape distances, the Kofun series in southern Kyushu was close to the Yayoi series in northern Kyushu as well as the West-Kofun and East-Kofun series. On the basis of bone and dental morphology, the Yayoi people in northwestern Kyushu are considered descendants of the Jomon people. However, the Yayoi people in northern Kyushu are generally thought to have been influenced by immigrants. Matsumura (1990) noted that the dental characteristics of the West-Kofun and East-Kofun series were closely related to the Yayoi immigrant people in general. Over all, the dental characteristics of the Kofun series of southern Kyushu are closer to those of the immigrant population than those of the native population. Therefore, the Kofun people in southern Kyushu should be considered influenced by the immigrant population.

Copolymers of 3-methacryloxypropyl tris(trimethylsiloxy) silane (SiMA) with methacrylate (MMA) and copolymers trimethylsilyl methyl methacrylate (TMSMMA) with vinyl acetate (VAc) were synthesized by radical polymerization. Membranes were cast from their solutions. Gas permeability, 10-1000 Barrer, of SiMA-MMA membranes was higher than that of TMSMMA-Vac membranes because of higher concentration of trimethylsilyl groups. Both apparent activation energies for gas permeability were very small compared to those of ordinary polymeric membranes. Poly(SiMA) is rubbery and poly(TMSMMA) is glassy at an ambient temperature. Copoly(SiMA-MMA) and copoly(TMSMMA-VAc) were shown to be random copolymers by the relationship between gas permeability coefficients and the molar ratio of each monomer. A series of copolymers in this investigation was shown to be a rare case of the polymer of which gas permeability increased in spite of the larger side chain, trimethylsilyl group, being introduced in the polymer chains.

Background: Irinotecan and gemcitabine are effective against non-small cell lung cancer. We conducted a phase I study of the combined use of irinotecan and gemcitabine in previously untreated patients with advanced non-small cell lung cancer to determine doselimiting toxicities and maximum tolerated dose. Methods: Patients were treated with irinotecan followed by gemcitabine on days 1 and 8 every 3 weeks. Gemcitabine dose was fixed at 1000 mg/m 2 , and irinotecan dose was increased from 60 mg/m 2 . Results: A total of 16 patients was enrolled. Maximum tolerated dose of irinotecan was determined up to level 3 (irinotecan 100 mg/m 2 ). In Japan, the maximum approved weekly dose of irinotecan is 100 mg/m 2 , so this was the dose that was used. Only very mild hematological and non-hematological toxicities were noted. Conclusion: Use of 100 mg/m 2 irinotecan followed by 1000 mg/m 2 gemcitabine on days 1 and 8 every 3 weeks warrants a phase II study.

BACKGROUND. The purpose was to determine the efficacy and toxicity of irinotecan and cisplatin with concurrent split-course thoracic radiotherapy (TRT) in locally advanced nonsmall-cell lung cancer. METHODS. Fifty patients fulfilling the following eligibility criteria were enrolled: chemotherapy-naive, good performance status (PS, 0-2), age

Introduction: Malignant pericardial effusion (MPE) causes cardiac tamponade and an extremely poor outcome unless it is well controlled. The effect of pericardial drainage and the intra-pericardial instillation of bleomycin on the control of MPE was examined in this prospective multi-institutional phase II trial. Methods: In eligible patients with cytologically defined MPE resulting from non-small cell lung cancer, the pericardial effusion of such cases was continuously drained. After complete drainage, 10 mg of bleomycin was then locally instilled via a catheter. The catheter was then removed if the total amount of drainage was less than 30 ml/day. If the catheter could not be removed within 5 days after treatment, bleomycin was administered one more time. Results: Among the 22 patients who entered this trial, the tube drainage catheter was successfully removed from 17 patients with one instillation, whereas four required such instillation twice and one required such instillation three times. No severe adverse events were observed, except for constrictive pericarditis, which resulted in the treatment-related death of one patient. The control rate of pericardial effusion was 95% ± 0.09 (95% confidence interval). No restoration of pericardial effusion was observed during the follow-up period or until death from any cause. Median survival time from the beginning of the protocol was 17.9 weeks. Conclusions: Pericardial drainage followed by the instillation of bleomycin was found to be a safe and effective method for the management of MPE associated with non-small cell lung cancer.

The natural history of lung adenocarcinoma with ground-glass opacity (GGO) remains undetermined. We describe a lung adenocarcinoma in which GGO transformed through a scar-like lesion over the long term into a solid nodule of poorly differentiated adenocarcinoma. Whether poorly differentiated lung adenocarcinoma can evolve from GGO-type adenocarcinoma is an important issue that requires clarification.

Vinorelbine alone and irinotecan alone have been shown to have efficacy against non-small cell lung cancer (NSCLC); each drug has different mechanisms of action. A phase I study using a combination of vinorelbine and irinotecan as first-line treatment for advanced NSCLC was done to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT).Previously untreated patients (or=75 years old) with Stage IIIB or IV NSCLC were enrolled. Based on a 4-week cycle, vinorelbine was given on days 1 and 8, and irinotecan was given on days 1, 8, and 15 intravenously. To prevent an injection site reaction to vinorelbine, the site was treated with topical clobetasol ointment, and the patients were given intravenous dexamethasone prior to vinorelbine treatment. DLT was defined as grade 4 neutropenia lastingor=4 days or febrile neutropenia, grade 4 thrombocytopenia,or=grade 3 non-hematological toxicities, or the need to cancel drug administration on both days 8 and 15.A total of 23 patients were enrolled. DLT was observed in 1 of 6 patients at level 3 (20 mg/m(2) vinorelbine, 50 mg/m(2 )irinotecan), in 2 of 3 at level 4 (25 mg/m(2), 50 mg/m(2)), and in 2 of 5 at modified level 4 (20, 60 mg/m(2)). Level 4 and modified level 4 were considered to be the MTD; dose level 3 was therefore recommended. DLTs included liver dysfunction, pneumonitis, colitis, and arrhythmia. Injection site reactions were mild. Hematological and non-hematological toxicities were mild and easily controlled.Use of 20 mg/m(2) vinorelbine on days 1 and 8 followed by 50 mg/m(2 )irinotecan on days 1, 8, and 15 every 4 weeks warrants a phase II study.

Among cases that had multiple renal arteries on one side, an inferior supernumerary renal artery was found in 24/270 cases (ca. 9%) on the right and in 19/270 cases (ca. 7%) on the left, together with the usual renal artery. We have noticed that there are correlations between their levels of origin from the aorta and their positional relation to the ureter and the inferior vena cava (IVC). An inferior supernumerary renal artery (InfRA) of lower origin passes in front of the IVC and behind the ureter. An InfRA of middle origin passes in front of both the IVC and the ureter. An InfRA of upper origin passes behind the IVC and in front of the ureter or renal pelvis. In addition there was a tendency for the lower origin type to have an ureteric branch, while the middle and upper origin types had a gonadal branch. These findings suggest that different derivations lead to the inferior supernumerary renal arteries.

A 54-year-old nonsmoker female developed atelectasis of the anterior basal segment of the right lower lobe. A non-pulsating endobronchial tumor was observed bronchoscopically obstructing the right basal bronchus. The tumor was confirmed on arteriography to be a saccular aneurysm of the right bronchial artery. The aneurysm was treated with bronchial artery embolization. Bronchial artery aneurysm, without a predisposing disease, is quite rare, but should be considered as an etiological factor of atelectasis.

Two examples of partial anomalous drainage of the pulmonary vein were detected at dissection. The first case was found in a 70-year-old female Japanese. An aberrant vein, approximately 6 mm in diameter, that derived from the upper lobe of the right lung was observed to drain into the superior vena cava at a point just below the entrance of the azygos vein. The other veins from the right lung gathered into two pulmonary veins and returned into the left atrium as usual. In the second case, which was found in an 80-year-old female Japanese, a connecting vein, approximately 8 mm in diameter, was found between the left superior pulmonary vein and the left brachiocephalic vein. In this case, although the direction of the blood flow within the connecting vein was not certain, it is probable that the blood passed from the pulmonary vein into the brachiocephalic vein, judging from the increase in the width of the latter vein. No other anomalies were found in the cardiovascular systems. At the occurrence of the anomalous drainage of the pulmonary veins in both cases, we suspected the role of the bronchial vein to be a communicating and boundary vein between the pulmonary and systemic circulations. The developmental background of these anomalies is also considered.

Purpose: Docetaxel and carboplatin have a broad spectrum of antitumor activity. We conducted a phase I study of docetaxel and carboplatin as second-line chemotherapy in previously treated non-small-cell lung cancer (NSCLC). This study aimed to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities in this second-line combination chemotherapy. Methods: Patients with advanced NSCLC were treated with escalating docetaxel doses in combination with a fixed-target area under the concentration-time curve (AUC) of 5 mg·min/ml of carboplatin on day 1 of a 3–4-week cycle. The carboplatin dose was determined by multiplying the AUC by the clearance predicted using the Chatelut formula. The docetaxel dose was escalated from 40 mg/m2 to the MTD by 10 mg/m2 increments. Results: A total of 16 patients previously treated with anticancer drugs were enrolled through three dose levels (40, 50 and 60 mg/m2 of docetaxel). All patients were assessable for toxicity and response. The MTD was docetaxel 60 mg/m2 with a carboplatin target AUC of 5 mg·min/ml, and the dose-limiting toxicities in two of four patients were neutropenia and thrombocytopenia. Overall, neutropenia and thrombocytopenia of grade 3/4 occurred in eight patients (50%) and three patients (19%), respectively. Four patients (25%) and two patients (13%) experienced both grade 1 diarrhea and dermatitis, respectively. Allergic reactions, fluid retention, pneumonitis, neurotoxicity and mucositis were not observed. Of 16 patients, 5 showed an objective response (response rate 31%; 95%CI 14–56%). Conclusions: The combination of docetaxel and carboplatin is a feasible and well-tolerated second-line chemotherapy regimen in the treatment of NSCLC. Docetaxel 50 mg/m2 under the carboplatin target AUC of 5 mg·min/ml using the Chatelut formula was the recommended dose for phase II study.

Background: Amrubicin is active in the treatment ofextensive-disease small cell lung cancer (ED-SCLC), and carboplatin is an analogue of cisplatin with less non-hematological toxicity. Purpose: To determine the efficacy and toxicity ofamrubicin and carboplatin combination chemotherapy for previously untreated patients with ED-SCLC. Patients and methods: Eligibility criteria were chemotherapy-naive ED-SCLC patients, performance status 0-1, age Results: Thirty-five patients were enrolled and 34 patients were eligible and assessable for response, toxicity and survival. Patients' characteristics are as follows: male/female = 26/8; performance status (PS) 0/1 = 4/30; median age (range) = 64 (41-75); stage IV = 34. Evaluation of responses were 6 complete response (CR), 21 partial response (PR), and 7 stable disease (SD) (response rate 79.4%, 95%CI 63.6-88.5%). Grade 3 and 4 leukopenia, neutropenia, and thrombocytopenia occurred in 59%, 82%, and 26%, respectively. There were no treatment-related deaths or pneumonitis. Three patients experienced hypotension as an amrubicin infusion reaction. The median progression-free survival time was 6.5 months. The median overall survival time and 1-, 2- and 3-year survival rates were 15.6 months, 63%, 28% and 7%, respectively. Conclusions: Amrubicin and carboplatin was effective and tolerable as chemotherapy for previously untreated patients with ED-SCLC. Further investigation of amrubicin and carboplatin is warranted.

e19038 Background: Previously, through measuring plasma trough levels of gefitinib on days 3(D3) and 8 (D8), we reported that a high D8/D3 ratio was independently associated with better PFS in pati...

Coccidioides immitis is a causative agent of coccidioidomycosis, which is one of the most dreadful mycosis because of its infectious and pathogenic nature. The endemic areas are in the southwestern parts of the United States and other semi-arid regions throughout the Western Hemisphere. During the early 1990s, the incidence of coccidioidomycosis in California increased dramatically, resulting in recognition for this mycosis as a reemerging infectious disease in the United States. The patients included a large number of non-informed visitors from non-endemic countries. Our report is on an imported case of primary pulmonary coccidioidomycosis. A 35-year-old Japanese male, after living in the United States for nine months, suffered from a combination of headache and fever. He was given a serological examination, and a chest radiograph in Phoenix, Arizona in the United States and was diagnosed as coccidioidomycosis. A daily dosage of 400 mg of fluconazole was administered and he returned to Japan. His headache and skin rash persisted and he was admitted to our hospital to evaluate the severity of his disease. There were no fungi cultured from neither bronchoalveolar nor cerebrospinal fluid and he was discharged. The patient had been treated with fluconazole and his symptoms, high-resolution CT and serological antibody titer were monitored. After 18 months, his clinical and radiological evolution was favorable and his serological IgM titer was below its sensitivity medication was stopped and there were no relapses.