Vassilis Georgoulias

A multicenter phase II study of docetaxel in combination with gefitinib in gemcitabine-pretreated patients with advanced/metastatic pancreatic cancer

Purpose: To evaluate the efficacy and tolerance of the docetaxel/gefitinib combination as second-line treatment in patients with advanced pancreatic cancer. Patients and Methods: Twenty-six patients pretreated with gemcitabine-based chemotherapy were enrolled in the study. Docetaxel (75 mg/m2, i.v.) was administered every 3 weeks for a maximum of 6 cycles and gefitinib (250 mg/day, p.o.) was given continuously. Results: Five (19.2%) patients achieved stable disease. The median duration of disease control was 4.8 months (range 1–13.2), the median time to disease progression 2.1 months (range 1–7.3) and the median survival time 2.9 months (range 1–13.9). Grade 3/4 neutropenia was recorded in 9 (34.6%) patients, although only 1 (3.8%) developed grade 2 febrile neutropenia. One (3.8%) patient experienced grade 3 fatigue and 2 (7.7%) grade 3 diarrhea. Grade 1/2 rash was observed in 13 (50%) patients. There were no treatment-related deaths. Conclusion: The docetaxel/gefitinib combination, although safe, has no activity as salvage treatment for advanced pancreatic cancer after failure of gemcitabine-based chemotherapy.

Multicenter Phase II Study of Gemcitabine and Oxaliplatin (GEMOX) as Second-Line Chemotherapy in Colorectal Cancer Patients Pretreated with 5-Fluorouracil plus Irinotecan

Purpose: To evaluate the efficacy and tolerance of the gemcitabine/oxaliplatin (GEMOX) combination as second-line chemotherapy for patients with advanced colorectal cancer (CRC) pretreated with an irinotecan (CPT-11)/5-fluorouracil (5-FU)/leucovorin (LV) regimen. Patients and Methods: Patients with documented disease progression during or after first-line treatment with CPT-11 and 5-FU/LV were enrolled. Gemcitabine (1,000 mg/m2 days 1 and 8) and oxaliplatin (100 mg/m2 day 1) were administered every 3 weeks. Results: Partialresponses were observed in 6 of the 34 (17.7%) patients enrolled (intention-to-treat analysis; overall response rate: 17.7%; 95% confidence interval 4.8–30.5%). Eight (23.5%) patients experienced disease stabilization and 20 (59%) disease progression (tumor growth control rate = 41.2%). The median duration of response was 5.5 months, and the median time to tumor progression 2.7 months. The median overall survival was 9.1 months (1-year survival rate: 44.0%). Grade 3 neutropenia and thrombocytopenia occurred in 18 and 15% of the patients, respectively. Other severe non-hematologic toxicities were rare. Conclusion: The interesting tumor growth control rate and the favorable toxicity profile of the GEMOX regimen in pretreated patients with advanced CRC strongly suggest that this regimen may provide an alternative therapeutic option for this group of patients.

Modified CAPOX (Capecitabine plus Oxaliplatin) Regimen Every Two Weeks as Second-Line Treatment in Patients with Advanced Colorectal Cancer Previously Treated with Irinotecan-Based Frontline Therapy

Background: To evaluate the efficacy and tolerance of capecitabine (CAP) given every other week and biweekly oxaliplatin (OX; modified CAPOX regimen) in patients with advanced colorectal cancer previously treated with irinote- can-based frontline chemotherapy. Methods: Sixty-seven patients were enrolled; the median age was 62 years and 62 (92.5%) had a performance status (ECOG) of 0–1. OX and CAP were administered at the dose of 100 mg/m2 on day 1 and 2,000 mg/m2 on days 1–7, respectively, every 2 weeks. Results: A total of 429 treatment cycles were administered. Grade 3/4 neutropenia and thrombocytopenia were observed in 4 (6%) and 2 (3%) patients, respectively. Febrile neutropenia complicated 1 treatment cycle. The main nonhematologic toxicities were grade 2/3 peripheral sensory neurotoxicity (10% of patients) and grade 3/4 diarrhea (7%). In an intention-to-treat analysis, 3 (4.5%) complete and 13 (19.4%) partial responses (overall response rate 24%) were observed. Seventeen (24.5%) patients had stable and 27 (40.3%) progressive disease. The median time to tumor progression and overall survival were 5 months and 11.3 months, respectively. Conclusions: The results indicate that the modified CAPOX regimen is safe and effective as salvage treatment in patients with advanced colorectal cancer who were previously treated with irinotecan-based frontline therapy.

Metronomic Chemotherapy in Non-Small-Cell Lung Cancer

Metronomic chemotherapy is an alternative approach for the administration of systemic chemotherapy that consists of the administration of low doses of a cytotoxic regimen without any interruptions. Endothelial cells of the tumor blood vessels are rapidly proliferating cells that could be affected with the metronomic use of chemotherapy. Indeed, it is strongly believed that this strategy inhibits vascular angiogenesis and subsequently tumor growth mainly through modulating the cancer microenvironment with favorable toxicity profile. In addition, immune suppression is a reality among the vast majority of cancer patients. T regulatory cells (Tregs) are the main representative of suppressive cells, and their increased expression in cancer has been associated with worse prognosis and tumor progression. Low doses of chemotherapeutic agents have been proven capable to restore the normal immune system function through the elimination of immune suppressive cells. Numerous studies have investigated the efficacy of metronomic strategy in NSCLC patients with very promising results. Several chemotherapeutic agents, such as vinorelbine, gemcitabine, cyclophosphamide, and docetaxel, have been tested as monotherapy or in combination with other drugs. Whether other mechanisms, such as tumor dormancy, are also involved in the effectiveness of metronomic administration of chemotherapy or if it is superior to conventional chemotherapy remains questionable, and further investigation is required.

Abstract P1-13-09: A multicenter randomized study comparing the dose dense G-CSF-supported sequential administration of FEC followed by docetaxel versus paclitaxel as adjuvant chemotherapy in women with axillary lymph node positive breast cancer.

Purpose: To compare the efficacy of dose dense docetaxel versus paclitaxel following FEC as adjuvant chemotherapy in node positive early breast cancer. Patients and treatment: Women 18–75 years old with histologically confirmed HER2-negative invasive breast carcinoma surgically resected with at least one infiltrated axillary lymph node and absence of metastatic disease were randomized to receive 4 cycles of fluorouracil (700mg/m2), epirubicin (75mg/m2), cyclophosphamide (700mg/m2) followed by 4 cycles of either docetaxel (75mg/m2) or paclitaxel (175mg/m2). All chemotherapy cycles were administered every 14 days with G-CSF support. Stratification was based on menopausal status, number of involved nodes and hormone receptor expression. The primary endpoint of the study was to compare the disease-free survival (DFS) at 3 years and 239 patients were scheduled to enroll on each arm. Results: Between 2004–2007, 481 women were randomized and received FEC followed by docetaxel (arm A; n=240) or paclitaxel (arm B; n=241). The median age was 55 years in both arms, premenopausal status 31.3% versus 32.8%, more than 10 involved axillary nodes in 12.9% versus 12.4%, histological grade 3 tumor in 36.3% versus 35.3% and hormone receptor negative disease in 14.6% versus 12% of patients in arms A and B, respectively. After a median follow up of 56.3 and 55.6 months (p = 0.3) for arms A and B, respectively, there were 42 (17.5%) versus 47 (19.5%) disease relapses (p = 0.5) and 20 (8.3%) versus 22 (9.1%) disease-related deaths (p = 0.7), respectively. The 3-year DFS rates were 88.1% versus 87.3% for arms A and B, respectively. Toxicity included grade 2–4 neutropenia in 31% versus 21% (p = 0.01), thrombocytopenia 3.5% versus 0.8% (p = 0.06), febrile neutropenia 2.1% versus 1.2% (p = 0.5), diarrhea 3.7% versus 2.5% (p = 0.4), neurotoxicity 2.9% versus 4.6% (p = 0.3) of patients in arms A and B, respectively. There were no toxic deaths. Conclusion: The dose dense administration with G-CSF support of FEC followed by either docetaxel or paclitaxel as adjuvant chemotherapy in women with node positive early breast cancer is well tolerated and results in a similar 3-year DFS rate. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-09.