ABSTRACT
Zoledronic acid (Zometa, Novartis, Basel, Switzerland) is a new generation of bisphosphonates (BPs) with demonstrated clinical benefit in breast and prostate cancer patients with bone metastases. The safety and efficacy of intravenous zoledronic acid in lung cancer patients was assessed. In 86 patients with newly diagnosed non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) and bone metastases, 4 mg of zoledronic acid was administered with rapid 15-minute intravenous infusion every 3-4 weeks. A total of 414 infusions were administered over a 24-month period during which a statistically significant decrease in serum calcium levels (p = 0.03) was observed. Serum alkaline phosphatase (ALP) also decreased but not significantly. With regard to clinical efficacy, 55 of our patients stabilized or reduced their need for analgesic treatment. No significant side-effects, including fever, hemodynamic instability and renal dysfunction, were seen. We conclude that the rapid infusion of zoledronic acid is safe and convenient for lung cancer patients even after the 3rd and 6th months follow-up.
Subject(s)
Bone Density Conservation Agents/administration & dosage , Bone Neoplasms/drug therapy , Bone Neoplasms/secondary , Diphosphonates/administration & dosage , Imidazoles/administration & dosage , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Adult , Aged , Bone Density Conservation Agents/adverse effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/secondary , Carcinoma, Small Cell/drug therapy , Carcinoma, Small Cell/secondary , Diphosphonates/adverse effects , Drug Administration Schedule , Female , Humans , Imidazoles/adverse effects , Infusions, Intravenous , Male , Middle Aged , Zoledronic AcidABSTRACT
Our study involves a preliminary phase II trial, which evaluates the activity, feasibility and tolerability of a sequential combination of docetaxel and gemcitabine followed by docetaxel and carboplatin, as first-line treatment for inoperable NSCLC. Twenty-six chemo-naïve patients aged less than 75 years with histologically or cytologically confirmed unresectable stage IIIB, IV or relapsed post-operative metastatic NSCLC were included in the study. Gemcitabine 1,250 mg/m(2) was administered and was followed by docetaxel 65 mg/m(2). Treatment was administered on days 1 and 14 in a 28-day cycle for three consecutive cycles. If patients had no progressive disease after three cycles of chemotherapy, they received another three cycles of docetaxel 65 mg/m(2) followed by carboplatin AUC5 on day 1 in a 21-day cycle. Recombinant human granocyte colony-stimulating factor (rhG-CSF) was given prophylactically. In addition, all patients received standard pre- and post- treatment with oral dexamethasone. Response rates at three cycles were: 19% achieved a partial response (PR), 46% had stable disease (SD) and 23% had progressive disease. At six cycles, 8% of the patients maintained PR, 19% showed SD and 35% had progressive disease. The median time-to-disease progression was 6 months. The median survival time of patients was 10 months while, at the end of the first year, the patients who managed to get through the complete therapy (20 patients) had a survival rate of 38%. This detailed analysis of 20 patients showed that 80% of the patients survived for up to 6 months, 38% up to 12 months and 19% for more than a year. The only risk factor associated with the hazard of death among the factors studied was the performance status of the patients. Patients with PS=0 presented a median survival time of 13 months and those with PS=1, it was only 9 months. Non-haematological and haematological toxic effects were generally mild to moderate and entirely manageable.
