Keiichi Fujiwara

Dramatic effect of ZD1839 (‘Iressa’) in a patient with advanced non-small-cell lung cancer and poor performance status

We describe the case of a 52-year-old Japanese woman with advanced adenocarcinoma of the lung, in whom once-daily treatment with 250 mg ZD1839 (Iressa) demonstrated a marked antitumour effect. She had initially achieved a partial response with cisplatin-based combination chemotherapy, but had subsequently progressed and had failed to respond to salvage chemotherapy. She had also received whole-brain irradiation for brain metastases. On admission, the patient was confined to bed due to dyspnoea and had rapidly progressing hypoxia secondary to lymphangitis carcinomatosa and a massive right pleural effusion. She was treated with oxygen supplementation and oral ZD1839, which, within a week, led to marked tumour regression and gradually improving dyspnoea. The main adverse event observed was a grade 2 rash. A month after starting ZD1839 treatment, the patient was discharged without the need for oxygen supplementation and had since returned to full-time work. This is a demonstration of ZD1839 producing a dramatic clinical response when administered to a patient with poor performance status who had received extensive prior treatment with cytotoxic agents.Iressa is a trademark of the AstraZeneca group of companies.

Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma

Purpose According to the World Health Organization (WHO) classification of pulmonary large cell neuroendocrine carcinoma (LCNEC), one of the neuroendocrine tumors of the lung, is considered as a variant of non-small cell lung carcinoma. The objective of this study was to investigate the treatment strategy for LCNEC.Methods We retrospectively reviewed the clinical information of 12 patients with LCNEC.Results Three patients with stage I disease underwent curative resection but all relapsed within 20xa0months. One with stage IIA disease underwent non-curative resection received adjuvant chemoradiotherapy (cisplatin plus etoposide) and is well with no evidence of recurrence. Two with stage IIIB disease received concurrent chemoradiotherapy. Both achieved partial response (PR) but relapsed within 2xa0months. One elderly patient with stage IIIA disease received vinorelbine alone and did not respond. Of five patients with stage IV disease, three received platinum-based chemotherapy but no patient achieved PR. Of five patients with gefitinib as salvage therapy, one achieved PR.Conclusions The prognosis of LCNEC is poor. To improve the outcome, we must evaluate the effectiveness of adjuvant or neoadjuvant therapy in patients with resectable disease. In addition, the evaluation of systemic and multimodality treatment strategies similar as in small cell lung cancer is worthy of consideration.

Clinical and pharmacokinetic study of docetaxel in elderly non-small-cell lung cancer patients

PurposeTo evaluate the usefulness and pharmacokinetics of docetaxel in the treatment of elderly patients with advanced non-small-cell lung cancer.Patients and methodsChemotherapy-naive elderly patients (aged at least 76xa0years) with locally advanced or metastatic non-small-cell lung cancer were accrued. Eligible patients received at least two cycles of docetaxel at a dose of 60xa0mg/m2 on dayxa01 over 1xa0h every 3xa0weeks. Patients who were considered ineligible for this study were also registered. Symptom control was assessed using a questionnaire during the treatment period. The pharmacokinetics of docetaxel were evaluated in the first cycle of chemotherapy.ResultsOf 35 elderly patients, 15 (43%) met the study eligibility criteria. The reasons for ineligibility consisted mainly of poor performance status, poor bone marrow function, and hypoxemia (six patients each). A total of 49 cycles of chemotherapy (median 2 cycles, range 1–12 cycles) were administered to the eligible patients, six of whom achieved a partial response (overall response rate 40%, 95% confidence interval 15–65%). The major toxicity was hematologic, with grade 3 or greater neutropenia and grade 3 neutropenic fever developing in 13 patients (87%) and five patients (33%), respectively. Symptoms, as assessed in terms of the symptom control score, did not clearly decline during the treatment period. The values (mean±SD) of Cmax, AUC0→inf, and t1/2 were 1.35±0.32xa0μg/ml, 1.79±0.52xa0μgxa0h/ml, and 4.1±2.3xa0h, respectively.ConclusionsAlthough the validity of the results of this study is limited due to the small sample size, docetaxel appears effective in selected elderly patients with advanced non-small-cell lung cancer.

Triple Combination Chemotherapy with Cisplatin, Docetaxel, and Irinotecan for Advanced Non-small Cell Lung Cancer: A Phase I/II Trial

Background: To determine the recommended dose and evaluate the response rate and toxicity of triplet chemotherapy using cisplatin, docetaxel, and irinotecan for non-small cell lung cancer (NSCLC) patients with stage IIIB or IV. Methods: A total of 65 patients (33 men and 32 women) with advanced NSCLC, a good performance status, and 65 years of age or younger were included in these phase I/II studies. The median age was 52 years. Most patients had performance status 1 (49/65) and stage IV disease (49/65). Adenocarcinoma was the most common tumor histology (55 patients). Cisplatin and docetaxel were given on day 1 and irinotecan on day 2; the cycles were repeated every 3 weeks. Results: In the phase I study, the maximum tolerated doses of combination cisplatin/docetaxel/irinotecan were, respectively, 80/60/60 (mg/m2) and the recommended doses for the phase II study were determined to be 60/60/60 (mg/m2), respectively. The dose-limiting toxicities were neutropenia, neutropenic fever, and diarrhea. In the phase II study, 157 cycles of chemotherapy were delivered to 49 patients (median three cycles per patient). The objective response rate was 57.1% (95% confidence interval: 43.1%–71.1%). The median survival time and the actual 2-, 3- and estimated 5-year survival rates were 17 months, 33%, 25%, and 18%, respectively. Grade 3/4 toxicities consisted of neutropenia (92%), neutropenic fever (45%), nausea/vomiting (27%), diarrhea (35%), and hepatic toxicity (2%); there were no cases of treatment-related death. Conclusion: This triplet chemotherapy has shown a promising activity against advanced NSCLC according to admission-based treatment with adequate supportive care. The principal toxicity was neutropenic fever, but supportive care should be explored to reduce this incidence.