Dose Escalating Study of Biweekly Gemcitabine and Carboplatin in Patients With Advanced Cancer
Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.American journal of clinical oncology (Impact Factor: 3.06). 11/2007; 30(5):481-6. DOI: 10.1097/COC.0b013e31804b45c3
Combination chemotherapy with gemcitabine and carboplatin administered on a 3-week cycle is used commonly in the treatment of cancer. The purpose of our study was to establish a safe dose of combined gemcitabine and carboplatin when administered on a biweekly schedule to patients with advanced solid tumors. Gemcitabine was given intravenously over 30 minutes followed by carboplatin also given intravenously over 30 minutes once every 2 weeks (one cycle). Five dose levels were examined, ranging from gemcitabine at 1250 mg/m2 to 2000 mg/m2 and carboplatin at an area under the curve of 2.5 to 3.0. Twenty-six patients were studied (18 male and 8 female) with a median age of 57 years (range, 41-83 years); ECOG performance status was 0 or 1 in 22 patients (85%); median number of prior chemotherapy regimens was 2 (range, 0-4); median number of cycles administered per patient was 3 (range, 1-9) with a total of 89 cycles. Two dose-limiting toxicities were observed. Delay in treatment was seen in a total of 8 cycles with 6 of the delays due to myelosuppression. Grade 3 or 4 hematologic toxicity rates were as follows: anemia in one cycle (1%), neutropenia in 13 cycles (15%), and thrombocytopenia in one cycle of chemotherapy (1%). There were no hospitalizations for neutropenic fever. Mild fatigue was the most common nonhematologic toxicity. The median time to progression was 40 days (mean, 49 days; range, 4-133 days). Of the 21 evaluable patients, partial response or stable disease was observed in 11 (42%). The maximum tested dose of gemcitabine at 2000 mg/m2 and carboplatin at area under the curve of 3.0 was well tolerated on a biweekly schedule. Our findings indicate that further investigation of this biweekly regimen is warranted in patients with advanced cancer.
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ABSTRACT: Fanconi anemia (FA) is characterized by pancytopenia, congenital malformations, and susceptibility to malignancies. We describe a 31-year-old man with FA, who had undergone bone marrow transplantation and whole body irradiation at the age 17 years for FA. Fourteen years later, he presented with squamous cell carcinoma of the bronchus intermedius in the right lung. The tumor was located next to the main pulmonary artery and between the superior and inferior pulmonary veins. Two cycles of neoadjuvant therapy were given in an attempt to decrease tumor size and avoid a potential right pneumonectomy. Treatment consisted of a 21-day cycle with carboplatin (area under the curve 3) given on day 1 and gemcitabine (1250 mg/m) on day 1 and 8. Because FA cells are hypersensitive to DNA crosslinking agents, we reduced the carboplatin dose to minimize treatment-related toxicity. The tumor regressed sufficiently to permit performance of a right middle and lower lobectomy. In our case, neoadjuvant therapy with gemcitabine and low-dose carboplatin exhibited antitumor activity with manageable side-effects, suggesting that this chemotherapy regimen can be safely and effectively used in the treatment of NSCLC in FA patients who have achieved hematopoietic reconstitution after bone marrow transplantation.
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ABSTRACT: BACKGROUND:: This study was initiated to assess the safety and efficacy of biweekly carboplatin and gemcitabine with bevacizumab in treatment-naive patients with advanced and metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS:: An open-label, nonrandomized phase II clinical trial was conducted. Treatment consisted of a biweekly cycle of gemcitabine, carboplatin, and bevacizumab for a maximum of 6 cycles. If no disease progression or intolerable side effects were observed, maintenance therapy with bevacizumab was continued until disease progressed. Progression-free survival, overall survival (OS), objective response rate, and the safety and tolerability of the therapy were assessed. RESULTS:: Treatment was administered to 35 patients with stage IIIB/IV NSCLC. Median age of the patients was 64.5 years, with 58% being male. Median number of cycles of treatment was 6 (range, 4 to 28 cycles); median number of days of treatment was 117 days (range, 43 to 451 d). Sixty-six percent of patients experienced grade ≥3 toxicities. Hypertension (19%) was the most common adverse event. Pulmonary hemorrhage (3%) and pulmonary abscess (3%) were the causes of treatment-related deaths. There were 48% patients with partial response, 23% with stable disease, and 29% with progressive disease. Median progression-free survival was 2.6 months [95% confidence interval (CI), 1.6-3.4], and median OS was 13.4 months (95% CI, 8.4-24). The 2-year OS rate was 30% (95% CI, 12%-51%). CONCLUSIONS:: Biweekly therapy with combination of carboplatin, gemcitabine, and bevacizumab in advanced inoperable NSCLC provided limited benefit and was associated with excessive toxicity. Further testing of this regimen is not recommended. CLINICALTRIALS.GOV IDENTIFIER:: NCT00400803.