N Shimizu

Anti-HER2 antibody enhances the growth inhibitory effect of anti-oestrogen on breast cancer cells expressing both oestrogen receptors and HER2

Anti-oestrogen is effective for the treatment of oestrogen receptor (ER)-positive breast carcinomas, butmost of these tumours become resistant to anti-oestrogen. It has been suggested that anti-oestrogen therapy may induce a HER2signalling pathway in breast cancer cells and this may cause resistance to anti-oestrogen. Thus, it is conceivable that combinedtherapy with anti-oestrogen and anti-HER2 antibody might be more effective. In the present study, we investigated the effect ofcombined treatment with a humanized anti-HER2 monoclonal antibody, rhumAbHER2 (trastuzumab), and an anti-oestrogen, ICI 182,780, onthe cell growth of three human breast cancer cell lines which respectively express different levels of ER and HER2. The combinedtreatment enhanced the growth inhibitory effect on ML-20 cells, which express a high level of ER and a moderate level of HER2, butshowed no additive effect on either KPL-4 cells, which express no ER and a moderate level of HER2, or MDA-MB-231 cells, which express no ER and a low level of HER2. It is also suggested that both the antibody and anti-oestrogen induce a G1–S blockade and apoptosis. These findings indicate that combined treatment with anti-HER2 antibody and anti-oestrogen may be useful for thetreatment of patients with breast cancer expressing both ER and HER2.

Preoperative concurrent chemoradiotherapy with cisplatin and docetaxel in patients with locally advanced non-small-cell lung cancer.

The objective of this study was to assess the feasibility and effectiveness of an induction chemoradiotherapy regimen followed by surgery in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). A total of 22 patients with LA-NSCLC were treated with induction chemoradiotherapy consisting of cisplatin (40 mg m−2) and docetaxel (40 mg m−2) given on days 1, 8, 29 and 36 plus concurrent thoracic irradiation at a dose of 40–60 Gy (2 Gy fraction−1 day−1). Surgical resection was performed within 6 weeks after completion of induction therapy. Objective response to the induction therapy was obtained in 16 patients (73%). In all, 20 patients (91%) underwent surgery and complete resection was achieved in 19 patients (86%). Pathological downstaging and pathological complete response were obtained in 14 (64%) and five (23%) patients, respectively. With a median follow-up period of 32 months, the calculated 3-year overall and progression-free survival rates were 66 and 61%, respectively. It is noteworthy that the 3-year overall survival rate in 14 patients achieving pathological downstaging was extremely high (93%). Toxicity was manageable with standard approaches. No treatment-related deaths occurred. This combined modality treatment is feasible and highly effective in patients with LA-NSCLC. The results warrant further large-scale study to confirm the effectiveness of this regimen.

Preoperative induction chemotherapy with cisplatin and irinotecan for pathological N2 non-small cell lung cancer

We conducted a phase I/II study to investigate whether the surgical resection after induction chemotherapy with cisplatin and irinotecan was feasible and could improve the treatment outcome for patients with pathological N2 non-small cell lung cancer. Fifteen patients with stage IIIA non-small cell lung cancer having mediastinal lymph node metastases proved by mediastinoscopy were eligible. Both cisplatin (60 mg m−2) and irinotecan (50 mg m−2) were given on days 1 and 8. Patients received two cycles of chemotherapy after 3–4 weeks interval. Induction was followed by surgical resection in 4–6 weeks. Patients who had documented tumour regression after preoperative chemotherapy received two additional cycles of chemotherapy and other patients received radiotherapy postoperatively. After the induction chemotherapy, the objective response rate was 73%. All the 15 patients received surgical resection and complete resection was achieved in 11 (73%) patients. There was no operation-related death and one death due to radiation pneumonitis during postoperative radiotherapy. The median time from entry to final analysis was 46.5 months, ranging from 22 to 68 months. The 5-year survival rate was 40% for all the 15 patients and it was 55% for the 11 patients who underwent complete resection. We conclude that the surgical resection after induction chemotherapy with cisplatin and irinotecan is feasible, and associated with low morbidity and high respectability.