Masao Ichiki

Phase 1 clinical study of cyclophilin B peptide vaccine for patients with lung cancer.

Cyclophilin B (CypB) possesses two antigenic epitopes (CypB84–92 and CypB91–99) recognized by HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes (CTLs). To determine the safety of CypB-derived peptides and its ability to generate antitumor immune responses, patients with advanced lung cancer received subcutaneous vaccinations of these peptides or their modified peptides. All 16 patients were vaccinated with CypB91–99 or its modified peptide, whereas only two patients were vaccinated with the modified CypB84–92, as immediate-type hypersensitivity to CypB84–92 or its modified peptide was observed in the remaining patients. No severe adverse events were associated with the vaccination. No significant increase in cellular responses to either peptides or tumor cells was observed in the postvaccination PBMCs by the conventional CTL assays in any patients tested. These results suggest that the vaccination of CypB91–99 peptide was safe, but failed to induce objective immune responses at this regimen.

Combination Chemotherapy with Irinotecan and Ifosfamide as Second-Line Treatment of Refractory or Sensitive Relapsed Small Cell Lung Cancer: A Phase II Study

This phase II study was conducted to investigate the efficacy and safety of irinotecan (CPT-11) and ifosfamide as second-line chemotherapy for relapsed small cell lung cancer (SCLC). Eligibility criteria included histologically or cytologically confirmed SCLC, prior chemotherapy including platinum + etoposide, and measurable or evaluable disease. CPT-11 (80 mg/m2) was administered intravenously on days 1, 8 and 15, while ifosfamide (1.5 g/m2) was given on days 1 through 3 every 4 weeks. Thirty-four patients (29 men) with a median age of 69 years (range 42–77) and a median Eastern Cooperative Oncology Group (ECOG) performance status of 1 (range 0–2) were enrolled. The response rate was 52.9% (95% confidence interval: 29.8–64.9%) with 2 complete responses and 16 partial responses. Our analyses of prognostic factors showed risk factors assessed before receiving second-line chemotherapy, which were the number of metastatic sites, performance status and the type of relapse. WHO grade 3–4 neutropenia was recorded in 52.9% of the patients, grade 3 diarrhea in 5.9%. The combination of CPT-11 and ifosfamide demonstrated clinical efficacy in relapsed SCLC with a favorable toxicity profile, particularly for performance status 0–1 and sensitive cases with only one metastatic site.

Chronic pulmonary scedosporiosis simulating aspergillosis

Abstract:  Scedosporium apiospermum, a ubiquitously distributed saprophyte, is emerging as an important pathogen in immunocompromised patients. We describe a 72‐year‐old patient with chronic S. apiospermum infection of the lung simulating aspergilloma. His medical history was unremarkable except that he had undergone partial lung resection as a treatment for pulmonary tuberculosis several decades previously. He had no underlying immunosuppressive conditions. This patient illustrates that pulmonary scedosporiosis is not confined to immunocompromised patients and that the clinical presentation may be indistinguishable from that of aspergilloma.

The usefulness of monomeric periostin as a biomarker for idiopathic pulmonary fibrosis

The natural course of idiopathic pulmonary fibrosis (IPF) is variable. Predicting disease progression and survival in IPF is important for treatment. We previously demonstrated that serum periostin has the potential to be a prognostic biomarker for IPF. Our aim was to use monomeric periostin in a multicenter study to evaluate its efficacy in diagnosing IPF and predicting its progression. To do so, we developed a new periostin kit to detect only monomeric periostin. The subjects consisted of 60 IPF patients in a multicenter cohort study. We applied monomeric periostin, total periostin detected by a conventional kit, and the conventional biomarkers—KL-6, SP-D, and LDH—to diagnose IPF and to predict its short-term progression as estimated by short-term changes of %VC and % DL, CO. Moreover, we compared the fraction ratios of monomeric periostin to total periostin in IPF with those in other periostin-high diseases: atopic dermatitis, systemic scleroderma, and asthma. Monomeric periostin showed the greatest ability to identify IPF comparable with KL-6 and SP-D. Both monomeric and total periostin were well correlated with the decline of %VC and % DL, CO. Clustering of IPF patients into high and low periostin groups proved useful for predicting the short-term progression of IPF. Moreover, the relative ratio of monomeric periostin was higher in IPF than in other periostin-high diseases. Measuring monomeric periostin is useful for diagnosing IPF and predicting its short-term progression. Moreover, the ratio of monomeric periostin to total periostin is elevated in IPF compared to other periostin-high diseases.

Detection of MAGE-4 protein in sera of lung cancer patients

We investigated the level of MAGE‐4 protein in sera of patients with primary lung cancer to understand better the biological roles of the MAGE proteins. MAGE‐4 protein was detected as a non‐degraded form in botb the supernatant of a MAGE‐4+ tumor cell line and in a patients serum. Serum level of the MAGE‐4 protein in lung cancer patients (n= 100, mean = 1.17 ng/ml) was significantly higher than that in either patients with benign pulmonary diseases (n= 80, 0.33 ng/ml) or healthy donors (n=68, 0.32 ng/ml). It was higher than the cutoff level (1.15 ng/ml) in 34 of 100 cancer patients, but not in anyone in the other groups.

Prognostic significance of febrile episodes in lung cancer patients receiving chemotherapy

The prognostic significance of neutropenic fever in lung cancer patients receiving chemotherapy with or without radiotherapy was investigated. Male patients and patients with squamous cell lung cancer had a higher incidence of febrile episodes than female patients and patients with other cell types, but the differences were not significant. Patients with a poor performance status had a significantly higher incidence of febrile episodes. An indwelling central venous catheter was an important risk factor for febrile episodes, indicating that bacteremia was one of the major causes of fever. The median survival time of the patients who developed febrile episodes during chemotherapy was significantly shorter than that of patients without fever (6.1 vs 12.0 months), whether or not cases of early death within 3 months were excluded (8.9 vs 13.1 months). The prevention of infectious complications during anticancer treatment by the use of rh G-CSF and the early initiation of antimicrobial chemotherapy, although the results are inconclusive, may be worthwhile.

Effect of add-on therapy of tiotropium in COPD treated with theophylline

Background Although combination therapy with bronchodilators is recommended for chronic obstructive pulmonary disease (COPD), there is insufficient evidence for the efficacy of some combinations of long-acting bronchodilators. Objective We investigated the effects of a combination therapy with tiotropium and theophylline in COPD patients. Methods In a 12-week, open-labeled, parallel-group randomized study, pulmonary functions and dyspnea scores were compared between the combination and theophylline alone therapy at baseline, and 4 and 8 weeks after randomization in COPD. Results Sixty-one COPD patients completed the trial (31 combination therapy, 30 theophylline alone; mean age 70 years; 58 males; mean dyspnea score 2.0 and forced expiratory volume in one second (FEV1) 1.5 L [62.5% predicted]). FEV1 in the combination group, but not in the theophylline alone, was significantly increased at 4 (1.56 ± 0.13 L, p < 0.001) and 8 weeks (1.60 ± 0.13 L, p < 0.001) from the baseline (1.40 ± 0.12 L). In the combination group, but not the theophylline alone group, the dyspnea score was significantly improved after 4 (p < 0.01) and 8 weeks (p < 0.05) compared with baseline. In 17 patients who did not receive theophylline at screening, treatment with 4 or 8 weeks of theophylline alone did not improve dyspnea score or FEV1. Conclusion Addition of tiotropium therapy to theophylline treatment can improve dyspnea and pulmonary function in COPD. Although this study did not assess whether there was any benefit of adding theophylline to patients treated with tiotropium, tiotropium can be a useful addition in COPD already treated with theophylline.

Phase II Study of Irinotecan and Ifosfamide in Patients with Advanced Non-Small Cell Lung Cancer

Objectives: This phase II study was conducted to investigate the efficacy and safety of irinotecan (CPT-11) and ifosfamide as first-line chemotherapy for advanced non-small cell lung cancer (NSCLC). Methods: Eligibility criteria included histologically or cytologically confirmed NSCLC (stage IIIb or IV), no prior treatment, and measurable or evaluable disease. CPT-11 (80 mg/m2) was administered intravenously on days 1, 8, and 15, while ifosfamide (1.5 g/m2) was given on days 1 through 3 every 4 weeks. Results: Forty-four patients (31 men) with a median age of 65 years (range 43–75) and a median ECOG performance status of 1 (range 0–2) were enrolled. The response rate was 29.5% [95% CI: 16.7–45.2%], with 13 partial responses. The median survival was 12.5 months, the median time to progression was 5.3 months, and the 1 and 2-year survival rates were 52.3 and 11.3%, respectively. Toxicity was generally mild; WHO grade 3–4 neutropenia was recorded in 38.6% of the patients, grade 3 diarrhea in 6.8%, and grade 3–4 nausea/vomiting in 0%. Conclusions: CPT-11 combined with ifosfamide demonstrated anti-tumor activity in advanced NSCLC, with response and survival rates similar to those of cisplatin-based chemotherapy but with a more favorable toxicity profile.

Lung adenocarcinoma metastasis to the male breast: a case report.

We report the case of a 60-year-old male patient who was diagnosed with metastasis from primary lung cancer to the breast. The patient presented with a mass in the right breast. Mammography, ultrasound, and magnetic-resonance imaging each suggested primary breast cancer. A core-needle biopsy of the right breast mass indicated poorly differentiated adenocarcinoma. A basic chest X-ray showed a shadow in the left upper lung. Thoraco-abdominal computed tomography revealed a mass with a diameter of 90 mm in the left superior region, the shape of which was indicative of primary lung cancer. A lung biopsy confirmed poorly differentiated adenocarcinoma. We diagnosed primary lung cancer with metastases to the bone, brain and right breast (cT2N3M1, stage IV) by imaging and histopathology. He was administered carboplatin (area under the curve 6 mg / ml) and paclitaxel (200 mg / m(2)) tri-weekly, and underwent gamma-knife treatment for the brain metastasis. The treatments reduced the primary tumor and the metastases. However, after completion of the fifth treatment cycle, he developed disseminated intravascular coagulation from septic shock, and died on the eleventh day after completing the fifth cycle of treatment. Although metastasis to the mammary gland is uncommon, especially among males, metastasis to the mammary gland should be considered when a mammary mass does not exhibit the typical characteristics of breast cancer. A correct diagnosis of metastasis to the mammary gland from lung cancer makes it possible to select the most appropriate treatment method.

Well-differentiated fetal adenocarcinoma of the lung: early-phase sequential high-resolution computed tomographic findings.

Well-differentiated fetal adenocarcinoma is a rare primary adenocarcinoma originating in the lung. We present an early phase case that was followed up for 2 years with chest roentgens and high-resolution computed tomography. Multicentric origin was suspected in the sequential high-resolution computed tomography study findings.