[en] The Uptake and metabolism of sugars by suspension-cultured Catharanthus roseus cells were investigated. Substantially all the sucrose in the culture medium was hydrolyzed to glucose and fructose before being taken up by the cells. The activity of invertase bound to cell walls, determined in situ, was high at the early stage of culture. Glucose was more easily taken up by the cells than was fructose. Tracer experiments using [U-¹⁴C]glucose and [U-¹⁴C]fructose indicated that glucose is a better precursor for respiration than fructose, while fructose is preferentially utilized for the synthesis of sucrose, especially in the early phase of cell growth. These results suggest that fructose is utilized for the synthesis of sucrose via the reaction catalyzed by sucrose synthase, prior to the phosphorylation by hexokinase or fructokinase

[en] From June 1989 through October 1990, concurrent chemotherapy and split course radiotherapy was evaluated in a prospective nonrandomized phase II trial for patients with inoperable locally advanced non-small cell lung cancer (NSCLC). Treatment schedule consisted of a total dose of 50 Gy in 25 fractions to the chest plus cisplatin (100 mg/m²) on days 1 and 29, mitonicin-C (8 mg/m²) on days 1 and 29 and vindesine (3 mg/m²) on days 1, 8, 29, 36. Sixty-five patients were entered into this trial and 61 (13 stage IIIA and 48 stage IIIB) of these patients were eligible. Although none of the patients achieved a complete response, 53 had a partial response for an overall response rate of 87% (95% CI 78-95%); median duration of response was 276 days. Seven patients showed no change and one showed progressive disease. Of 53 responders, 35 relapsed. The overall one-, 2- and 3-year survival rates are 60%, 37% and 28%, respectively, and the median survival was 450 days. The most frequent side effect was bone marrow suppression; grade 3 of leukocytopenia occurred in 40 (32%) and grade 4 occurred in 76 (61%) during a total of 125 courses. There were two treatment-related deaths (one due to pneumonitis and the other due to pneumothorax and pulmonary infection). In conclusion, a high response rate was achieved, although local control was not sufficient. (N.K.)

[en] The cornerstone of treatment for small-cell lung cancer is cisplatin-based combination chemotherapy. Meta-analysis of several randomized trials demonstrated that combined modality treatment with chemotherapy and thoracic radiotherapy increases survival of patients with limited-stage small-cell lung cancer. Early timing of twice-daily thoracic radiotherapy combined with cisplatin and etoposide showed the best results. Prophylactic cranial irradiation is recommended for patients who achieved complete remission with chemoradiotherapy. A randomized trial comparing etoposide and cisplatin with irinotecan and cisplatin following etoposide and cisplatin plus concurrent accelerated hyperfractionated thoracic irradiation for limited-stage small-cell lung cancer is ongoing. (author)

[en] Thymic carcinoma is a rare mediastinal neoplasm with poor prognosis. Although the clinical benefit of chemotherapy for thymic carcinoma is controversial, cisplatin-based chemotherapy with or without radiation therapy is ordinarily adopted in advanced cases. We evaluated the clinical outcome of platinum-based chemotherapy with or without radiation therapy in unresectable thymic carcinoma patients. Ten patients with unresectable thymic carcinoma were treated with platinum-based chemotherapy with or without radiation therapy in the National Cancer Center Hospital between 1989 and 1998. We reviewed the histological type, treatment, response and survival of these patients. Four of the 10 patients responded to chemotherapy and both the median progression-free survival period and the median response duration were 6.0 months. The median survival time was 11.0 months. There was no relationship between histological classification and prognosis. Platinum-based chemotherapy with or without thoracic radiation is, regardless of tumor histology, marginally effective in advanced thymic carcinoma patients, giving only a modest tumor response rate and short response duration and survival. (author)

No abstract available

[en] Pretreatment computerized tomography (CT) films of the chest was studied to clarify the influence of interstitial shadow on developing interstitial lung disease (ILD). Eligible patients were those lung cancer patients who started to receive first-line chemotherapy between October 2001 and March 2004. Patients who received thoracic radiotherapy to the primary lesion, mediastinum, spinal or rib metastases were excluded. We reviewed pretreatment conventional CT and plain X-ray films of the chest. Ground-glass opacity, consolidation or reticular shadow without segmental distribution was defined as interstitial shadow, with this event being graded as mild, moderate or severe. If interstitial shadow was detected on CT films of the chest, but not via plain chest X-ray, it was graded as mild. Patients developing ILD were identified from medial records. A total of 502 patients were eligible. Mild, moderate and severe interstitial shadow was identified in 7, 8 and 5% of patients, respectively. A total of 188 patients (37%) received tyrosine kinase inhibitor (TKI) treatment, namely gefitinib or erlotinib. Twenty-six patients (5.2%) developed ILD either during or after chemotherapy. Multivariate analyses revealed that interstitial shadow on CT films of the chest and treatment history with TKI were associated with the onset of ILD. It is recommended that patients with interstitial shadow on chest CT are excluded from future clinical trials until this issue is further clarified, as it is anticipated that use of chemotherapeutic agents frequently mediate onset of ILD in this context. (author)

[en] The aim of combined modality treatment of lung cancer is to improve control of both local and metastatic disease. Retrospective reviews of the combined RT and CT modality in limited-stage small cell lung cancer (SCLC) showed an improvement of median survival and long term survival compared with CT alone. Among reports of 7 prospective trials in which patients were randomized so as to receive CT alone or CT with chest irradiation, combined modality treatment significantly increased the CR rate in 3/3, and the overall survival was significantiy prolonged in 3/7. Concurrently combined modality treatment has a modest survival benefit in limited stage SCLC. Our phase 2 study combining RT with cisplatin-containing CT showed better improvement of response and survival than CT alone in non-small cell lung cancer (NSCLC). Four reports of prospective randomized studies have been performed to determine whether combined RT and combination chemotherapy might be better than RT alone in limited-stage NSCLC. Two of these studies demonstrated a survival and response advantage for the combined modality treatment. However, this approach for NSCLC reported so far has been disappointing, because of relative lack of effectiveness of the present CT. (author)

[en] 

Background

Idiopathic interstitial pneumonias (IIPs) are associated with increased risk of lung cancer. In Japan, acute exaberation of IIPs induced by anticancer treatment is a critical issue. For this reason, there is limited available evidence regarding the optimal treatment approach for lung cancer patients complicated with IIPs. Our previous prospective pilot study demonstrated the safety and efficacy of weekly paclitaxel in combination with carboplatin for advanced non-small-cell lung cancer (NSCLC) with IIPs. The current study was conducted to confirm the results of the same combination therapy used in a larger patient population.

Methods

Chemotherapy-naïve patients with advanced stage or post-operative recurrent NSCLC patients complicated by IIPs were enrolled. Patients received paclitaxel (100 mg/m²) on days 1, 8, and 15, and carboplatin (AUC 5.0) once every 4 weeks.

Results

Thirty-three of 35 enrolled patients were evaluable for analysis and received a median of four treatment cycles (range 1–6). Four patients (12.1%; 95% confidence interval 3.4–28.2%) had acute exacerbation (AEx)-related IIPs to the study treatment. However, no fatalities due to AEx were observed. The overall response was 69.7%. The median progression-free survival, median survival time, and 1-year survival were 6.3 months, 19.8 months, and 55.4%, respectively.

Conclusions

The efficacy of carboplatin plus weekly paclitaxel treatment for advanced NSCLC patients with IIPs was comparable to that of conventional chemotherapy in advanced NSCLC patients without IIPs. Moreover, the primary endpoint was set to the frequency of treatment-related acute exacerbation, and the primary endpoint was met. These results suggest that patients with advanced NSCLC complicated by IIPs may benefit from this combination chemotherapy.

[en] Purpose: To determine the maximum tolerated dose in concurrent three-dimensional conformal radiotherapy (3D-CRT) with chemotherapy for unresectable Stage III non–small-cell lung cancer (NSCLC). Patients and Methods: Eligible patients with unresectable Stage III NSCLC, age ≥20 years, performance status 0–1, percent of volume of normal lung receiving 20 GY or more (V₂₀) ≤30% received three to four cycles of cisplatin (80 mg/m² Day 1) and vinorelbine (20 mg/m² Days 1 and 8) repeated every 4 weeks. The doses of 3D-CRT were 66 Gy, 72 Gy, and 78 Gy at dose levels 1 to 3, respectively. Results: Of the 17, 16, and 24 patients assessed for eligibility, 13 (76%), 12 (75%), and 6 (25%) were enrolled at dose levels 1 to 3, respectively. The main reasons for exclusion were V₂₀ >30% (n = 10) and overdose to the esophagus (n = 8) and brachial plexus (n = 2). There were 26 men and 5 women, with a median age of 60 years (range, 41–75). The full planned dose of radiotherapy could be administered to all the patients. Grade 3–4 neutropenia and febrile neutropenia were noted in 24 (77%) and 5 (16%) of the 31 patients, respectively. Grade 4 infection, Grade 3 esophagitis, and Grade 3 pulmonary toxicity were noted in 1 patient, 2 patients, and 1 patient, respectively. The dose-limiting toxicity was noted in 17% of the patients at each dose level. The median survival and 3-year and 4-year survival rates were 41.9 months, 72.3%, and 49.2%, respectively. Conclusions: 72 Gy was the maximum dose that could be achieved in most patients, given the predetermined normal tissue constraints.

[en] Lung adenocarcinoma patients with EGFR gene mutations have shown a dramatic response to gefitinib. However, drug resistance eventually emerges which limits the mean duration of response. With that in view, we examined the correlations between MET gene status as assessed by fluorescence in situ hybridization (FISH) with overall survival (OS) and progression-free survival (PFS) in adenocarcinoma patients with EGFR gene mutations who had received gefitinib therapy. We evaluated 35 lung cancer samples with EGFR mutation from adenocarcinoma patients who had received gefitinib. Gene copy numbers (GCNs) and amplification of MET gene before gefitinib therapy was examined by FISH. MET protein expression was also evaluated by immunohistochemistry (IHC). FISH assessment showed that of the 35 adenocarcinoma samples, 10 patients (29%) exhibited high polysomy (5 copies≦mean MET per cell) and 1 patient (3%) exhibited amplification (2≦MET gene (red)/CEP7q (green) per cell). IHC evaluation of MET protein expression could not confirm MET high polysomy status. The Eleven patients with MET FISH positivity had significantly shorter progression-free survival (PFS) and overall survival (OS) than the 24 patients who were MET FISH-negative (PFS: p = 0.001 and OS: p = 0.03). Median PFS and OS with MET FISH-positivity were 7.6 months and 16.8 months, respectively, whereas PFS and OS with MET FISH-negativity were 15.9 months and 33.0 months, respectively. Univariate analysis revealed that MET FISH-positivity was the most significant independent factor associated with a high risk of progression and death (hazard ratio, 3.83 (p = 0.0008) and 2.25 (p = 0.03), respectively). Using FISH analysis to detect high polysomy and amplification of MET gene may be useful in predicting shortened PFS and OS after Gefitinib treatment in lung adenocarcinoma. The correlation between MET gene status and clinical outcomes for EGFR-TKI should be further evaluated using large scale samples