Safety Of Dose-dense Chemotherapy Research Articles

Efficacy and safety of dose-dense chemotherapy in urothelial carcinoma.

We conducted a meta-analysis to assess the efficacy and safety of dose-dense chemotherapy in the treatment of patients with urothelial carcinoma. A systematic search was conducted in PubMed, Medline, Embase, Web of Science and Cochrane Collaboration's Central register of controlled trials (CENTRAL) for relevant articles. Data was obtained from 10 trials with a total of 1093 patients. The pooled pathologic complete response (pCR) was 27.8% in the ten studies with a full cohort of 684 patients who received dose-dense methotrexate, vinblastine, adriamycin and cisplatin (dd-MVAC). In the controlled trials, although the difference was not significant, the pCR rate in the dd-MVAC group has a trend of increase (odds ratio (OR) 1.52; 95% confidence interval (CI) 0.78-2.98, P = 0.22) compared with classic MVAC group. A significant improvement of overall survival (OS) (hazard ratio (HR) 0.77, 95% CI 0.61–0.97, p = 0.03) was also observed. Hematologic toxicities were the most frequent grade ≥ 3 toxicities including neutropenia/febrile neutropenia (17.5%), anemia (9.4%) and thrombocytopenia (6.1%). Compared with the classic MVAC group, dd-MVAC was associated with significantly decreased risks of all-grade adverse events (AEs) such as anemia (OR 0.457, 95% CI 0.249–0.840, p = 0.012), febrile neutropenia (OR 0.398 95% CI 0.233–0.681, p = 0.001), and neutropenia (OR 0.373, 95% CI 0.201–0.691, p = 0.002). In conclusion, dose-dense chemotherapy was effective and tolerable in patients with urothelial carcinoma, which could be considered as a reasonable therapeutic option.

Final analysis of efficacy and safety of dose-dense chemotherapy with modified TCF regimen (TCF-dd) in elderly patients (pts) with metastatic gastric cancer (MGC).

e15086 Background: Gastric cancer is more common in elderly pts with its highest incidence around the seventh decade of life. Most oncologists are reluctant to treat this population with the most active polichemotherapy combinations because of safety concerns. Subgroup analyses of elderly pts enrolled in European studies show limited and conflicting data.We previously reported on the feasibility and high activity of a dose-dense TCF regimen (Tomasello 2010). This is a retrospective analysis of efficacy and safety of this schema in the elderly pts subgroup (≥ 65 years). Methods: From Nov 2004 to Jan 2013, 119 consecutivepts with MGC, PS 0-2, not previously treated, received Docetaxel 70 mg/m2 d1, Cisplatin 60 mg/m2 d1, l-Folinic Acid 100 mg/m2 d1-2, followed by 5-FU 400 mg/m2 bolus d1-2, and then 600 mg/m222 h c.i. d1-2, every 2 weeks, plus Pegfilgrastim 6 mg on day 3. Pts aged ≥ 65 years (60) received the same schedule with doses reducted by 30%. Results: Overall pts characteristics: 76% male, 24% female; median age: 65, range 31-81. A median of 4 cycles was administered. 102 pts were evaluable for response (86%) and all for toxicity. In pts aged ≥ 65 y, we observed 5 CR (8%), 26 PR (43%), 10 SD (17%) and 7 PD (12%); in younger pts: 3 CR (5%), 32 PR (54%), 9 SD (15%) and 10 PD (17%); ORR by ITT was 56% (95% CI 45-64). Median OS was 11,2 months (95% CI 9,4-14,1); in elderly and younger pts was 11,2 (95% CI 7,3-15,1) and 11,8 (95% CI 9,2-16,2), respectively. Out of 48 evaluable pts aged ≥ 65 years, 24 (50%) were treated at full doses without any delay. In the elderly most frequent grade 3-4 toxicities were: neutropenia (13%, p<0.0001), leucopenia (7%), thrombocytopenia (18%), anemia (3%, p=0.02), febrile neutropenia (8%), asthenia (27%), diarrhea (10%), nausea/vomiting (10%) and hypokalemia (17%); in the younger: neutropenia (56%), leucopenia (31%), thrombocytopenia (22%), anemia (15%), febrile neutropenia (15%), asthenia (41%), diarrhea (15%), nausea/vomiting (22%) and hypokalemia (20%). Conclusions: This study shows that elderly pts can be safely treated with a TCF-dd regimen with a 30% dose reduction achieving similar efficacy results as younger pts with lesser toxicity.

693P - Efficacy and Safety of Dose-Dense Chemotherapy with Modified TCF Regimen (TCF-DD) in Elderly Patients with Metastatic Gastric Cancer (MGC)

ABSTRACT Background GC is more common in elderly patients (pts). Most oncologists are reluctant to treat this pts population with the most active poli-chemotherapy combinations because of safety concerns. Subgroup analysis of elderly pts enrolled in European studies show limited and conflicting data. We previously reported on the feasibility and high activity of a dose-dense TCF regimen (TCF-dd) (Tomasello 2010). This study aims to evaluate the efficacy and safety of this schema in the elderly pts subgroup (≥ 65 years). Methods From 11/04 to 05/12, 111 consecutive pts with MGC (median age 65, range 31-81) were enrolled in a single-centre phase II study. Pts received Docetaxel 70 mg/m2 d1, CDDP 60 mg/m2 d1, l-AF 100 mg/m2 d1-2 followed by 5-FU 400 mg/m2 bolus d1-2, and then 600 mg/m2 as a 22h c.i. d1-2, q2w, plus G-CSF d3. Pts ≥ 65y (56) received the same schedule reduced by 30%. Results 96 pts evaluable for response and all for toxicity. In pts ≥ 65y we observed 4 CR (7%) 25 PR (45%) 10 SD (18%) 7 PD (13%); in younger pts: 2 CR (4%) 30 PR (55%) 9 SD (16%) 9 PD (17%); ORR by ITT 56% (95% IC 45-64). Median OS was 11.9 months (9,4-14,8); in elderly and younger pts 11,2 (8,4-11,1) and 12,7 (9-16,5) respectively. Out of 48 evaluable pts ≥ 65y, 26 (54%) were treated at full doses without any delay. In the elderly most frequent G3-4 toxicities were neutropenia (14%) thrombocytopenia (15%) febrile neutropenia (7%) asthenia (27%) and hypokalemia (17%); in the younger: neutropenia (56%) thrombocytopenia (21%) febrile neutropenia (16%) asthenia (43%) hypokalemia (21%). Conclusions This study shows that elderly pts can be treated with a TCF-dd regimen reduced by 30% achieving similar efficacy results of younger patients with lesser toxicity. Disclosure All authors have declared no conflicts of interest.