Efficacy Of Dose-dense Chemotherapy Research Articles

Efficacy of dose-dense chemotherapy as first-line treatment of advanced ovarian cancer patients after non-optimal debulking.

e18066 Background: Patients with advanced ovarian cancer have unfavorable prognosis after primary debulking surgery if the size of residual tumor exceeds 1 cm. The optimal approaches to systemic treatment of these patients remain unknown. We evaluated the efficacy and safety of dose-dose chemotherapy in frontline treatment of ovarian cancer patients after upfront non-optimal debulking surgery. Methods: This was a non-randomized single-arm phase II trial. We enrolled patients with advanced (FIGO III-IV) epithelial ovarian who underwent non-optimal upfront debulking surgery with residual tumor size > 10 mm. All patients were treated with dose-dense chemotherapy (ie, paclitaxel 80 mg/m2 day 1, 8, 15 + carboplatin AUC6 day 1, cycled every 21 days – 6 cycles). Patients in historical control arm received standard chemotherapy with paclitaxel 175 mg/m2 day 1 + carboplatin AUC6 day 1, cycled every 21 days – 6 cycles. No patient in experimental or control arm received front-line bevacizumab or PARP inhibitors. The primary endpoint of the trial was progression-free survival (PFS). According to the historical data of our department, 1-year PFS in this category of patients equals to 51%. To increase 1-year PFS to 70%, 40 patients should be enrolled with α = 0.05 and β = 0.20 and estimated data loss for 10% of patients. Results: The study enrolled 40 patients to dose-dense chemotherapy arm, control arm included 86 patients. The trial arms were balanced in terms of age, performance status and other characteristics. Median follow-up was 28.8 months. The 1-year PFS was 76.9% compared to 51% in historical arm, median PFS was 19.8 months and 12 months respectively (HR 0.61; 95% CI 0.39-0.95; p = 0,03). The 1-year overall survival rate was 92.3% with median OS not reached with specified follow-up period. Severe neutropenia, anemia, thrombocytopenia was observed in 82.1%, 53.8%, 15.3% of patients, respectively. Conclusions: The results of the study showed high efficacy of dose-dose chemotherapy as front line of treatment for advanced ovarian cancer patients after non-optimal upfront debulking surgery but one should consider high toxicity of this regimen.

186P - Efficacy of dose-dense (DD) adjuvant chemotherapy (CT) in hormone receptor positive/HER2-negative early breast cancer (BC) patients (pts) according to immunohistochemically (IHC) defined luminal subtypes: An exploratory analysis of the GIM2 trial

BackgroundDD adjuvant CT improves disease free survival (DFS) and overall survival (OS) in high-risk, hormone receptor positive BC. Luminal A and luminal B subtypes have different sensitivity to (neo)adjuvant chemotherapy; however, their role in predicting DD efficacy in clinically high-risk setting is uncertain. This exploratory analysis of the GIM2 trial (Del Mastro et al, Lancet 2015) evaluated DD efficacy according to IHC defined luminal subtypes. MethodsIn the GIM2 trial, pts with node-positive early BC were randomized to receive 4 cycles of (fluorouracil) epirubicin/cyclophosphamide every 2 (DD) or every 3 (standard interval [SI]) weeks followed by 4 cycles of DD or SI paclitaxel. Luminal A-like and luminal B-like BC were identified according to 13h St Gallen definition as having a Ki67<20% and a PgR>/=20% (luminal A-like), and a Ki67>/=20% and/or a PgR<20% (luminal B-like). Pts with HER2-positive BC were excluded. The efficacy of DD CT in terms of DFS and OS was compared between the two subtypes. ResultsOf 2,003 pts enrolled in the GIM2 trial, 401 had luminal A-like and 657 luminal B-like BC. After a median follow-up of 8 years, DFS was 81.1% (95% Confidence Intervals [CI] 76.6-84.7) and 70.6% (66.6-74.1) in luminal A-like and B-like BC, respectively; OS was 91.6% (88.1-94.1) and 85% (81.7-87.7), respectively. There was no significant interaction between treatment and luminal subtypes (pinteraction=0.416 for DFS and pinteraction=0.313 for OS); however, the effect of DD CT appeared to be greater in luminal-B like BC (see table below).Table186PTable8 year DFS SI8 year DFS DDHR (95% CI)luminal A-like81.680.60.86 (0.56-1.30)luminal B-like66.874.70.74 (0.55-0.98)8 year OS SI8 year OS DDLuminal A-like92.990.60.88 (0.47-1.67)luminal B-like80.889.40.61 (0.40-0.93) ConclusionsThese long-term results confirm the prognostic value of IHC-defined luminal subtypes, with luminal B-like bearing a worse prognosis. In clinically high-risk, hormone receptor positive BC, luminal B-like subtype benefits more from DD CT both in terms of DFS and OS. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureM. Lambertini: Honoraria (self), speaker honoraria: Theramex; Advisory / Consultancy: Teva. M. De Laurentiis: Advisory / Consultancy: Pfizer; Advisory / Consultancy: Novartis; Advisory / Consultancy: Eisai; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Roche; Advisory / Consultancy: Celgene. S. De Placido: Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Eisai; Honoraria (self): Novartis; Honoraria (self): Celgene; Honoraria (self): Eli Lilly. F. Montemurro: Honoraria (self), speaker honoraria: AstraZeneca; Honoraria (self), speaker honoraria: Pfizer; Honoraria (self), speaker honoraria: Novartis; Honoraria (self), speaker honoraria: Eli Lilly; Honoraria (self), Travel / Accommodation / Expenses, speaker honoraria, travel grant: Roche. L. Del Mastro: Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Ipsen; Honoraria (self): Roche-Genentech; Honoraria (self): Takeda; Honoraria (self): Eli Lilly. All other authors have declared no conflicts of interest.

First-line dose-dense chemotherapy with docetaxel, cisplatin, folinic acid and 5- fluorouracil (DCF) plus panitumumab (P) in patients with locally advanced or metastatic cancer of the stomach or gastroesophageal junction (GEJ): A phase II multicenter trial.

146 Background: Gastric cancer is a highly aggressive disease. No established standard first-line regimens are currently available. Aim of this study is to evaluate efficacy of dose-dense chemotherapy with DCF combined with P in patients (pts) with locally advanced or metastatic cancer of the stomach or GEJ. Methods: HER2 negative, ECOG PS 0-1, not previously treated pts, received up to 4 cycles of therapy with Panitumumab 6 mg/kg d 1, Docetaxel 60 mg/m2 d 1, Cisplatin 50 mg/m2 d 1, L-Folinic acid 100 mg/m2 d 1 and 2, followed by 5-FU 400 mg/m2 bolus d 1 and 2, and then 600 mg/m2 as a 22 h c.i. on d 1 and 2, every 2 weeks, plus Pegfilgrastim 6 mg on d 3. Pts aged ≥ 65 years were treated with the same chemotherapy schedule with a dose reduction by 30%. Pts with disease control after 4 cycles, received P until progression. Results: From 05/2010 to 01/2014, 52 consecutive pts were enrolled (75% M, 25% F; median age: 64.5 y, range: 42-75; metastatic 90%, locally advanced inoperable 10%; 96% adenocarcinoma; 13 pts with GEJ cancer). Primary end point was overall response rate (ORR). At 31 Aug 2014 cut-off date, 1 pt is still on treatment, 2 lost at f-up, 11 alive and 39 dead. 50 pts evaluable for response and all for toxicity. A median of 4 cycles (range 0-6) was administered. 3 CR, 29 PR, 10 SD and 8 PD were observed, for an ORR (by ITT) of 62% (95% CI, 48%-75) and a DCR of 81%. 26 pts entered the maintenance phase with only P and received a median 7.3 cycles (range 1-46). Median TTP was 4.8 months (95% CI, 4.1-6.9) and median OS was 9.4 months (95% CI, 7.4- 11.6). Most frequent grade 3-4 toxicities were: leucopenia (29%), neutropenia (19%), febrile neutropenia (13%), anemia (10%), asthenia (27%), mucosytis (13%), anorexia (17%), nausea/vomiting (12%), diarrhea (15%), ipokalemia (12%), and skin rash (25%). Two toxic deaths were registered (pulmonary aspergyllosis due to febrile neutropenia and gastric hemorrhage). Conclusions: Dose-dense chemotherapy combined with P is a very active regimen in gastric cancer. Due to a not negligible toxicity profile, it may represent a treatment option in neoadjuvant setting. Clinical trial information: 2009-016962-10.

Dose-dense neoadjuvant chemotherapy in breast cancer

807 Background: Neo-adjuvant chemotherapy has been proven to increase the rate of breast-conservation and represents the standard of care in patients with locally advanced breast cancer. Dose-dense chemotherapy has been shown to improve clinical outcomes in the adjuvant setting in node positive patients. We report here on the efficacy of dose-dense chemotherapy in the neo-adjuvant setting. Methods: We allocated 53 breast cancer patients to receive neo-adjuvant chemotherapy, because of locally advanced disease (T4 or N2+) or in the aim of maximizing breast conservation. All patients received doxorubicin (A) 60 mg/m2, cyclophosphamide (C) 600 mg/m2 and paclitaxel (T) 175 mg/m2, administered as concurrent AC x 4 every 2 weeks followed by T x 4 every 2 weeks. All patients received G-CSF, at an initial dose of 300 mcg, commencing on day 5 for 5 days. Nodal status was evaluated by physical examination, ultrasound, core-needle biopsy or sentinel biopsy prior to chemotherapy. Results: Median age of the patients was 45 (range 30–62), 77.5% were pre-menopausal and 8 of them presented with locally advanced disease while 45 had operable disease. The majority (90%) had hormone receptor (HR) positive tumors. Four patients discontinued the protocol because of toxicity. Response was evaluated in 49 patients (92%) who completed 8 courses of treatment and underwent surgery. Clinical complete response was observed in 10 (18%) and clinical partial response was observed in 34 (72%) of these patients. Overall, 39/49 patients (80%) underwent breast conserving surgery. Importantly, seven of the nine women who presented with locally advanced disease, underwent lumpectomy. Pathologic complete response was observed in the breast in 9 (18%), in the lymph nodes in 16 (33%) and in breast and lymph nodes in 6 (12%) of the 49 patients. Of the 53 patients, five had grade 3/4 hematological toxicity, two experienced Grade 3/4 nausea and only one had grade 4 vomiting. Conclusions: In this population of patients with mainly HR positive disease, dose-dense primary chemotherapy provided a feasible and safe short-duration treatment, yielded high clinical response rates and thus allowed conduction of breast conserving surgery in the vast majority of the patients. No significant financial relationships to disclose.