Sequential chemotherapy with dose-dense docetaxel, cisplatin, folinic acid and 5-fluorouracil (TCF-dd) followed by combination of oxaliplatin, folinic acid, 5-fluorouracil and irinotecan (COFFI) in metastatic gastric cancer: Results of a phase II trial
Dalla Chiesa M.,Azienda Ospedaliera di Cremona |
Dalla Chiesa M.,Concordia Medical |
Tomasello G.,Azienda Ospedaliera di Cremona |
Buti S.,Azienda Ospedaliera di Cremona |
And 5 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2011
Purpose: To evaluate a new strategy of two sequential, intensified chemotherapy regimens in metastatic gastric cancer. Patients and methods: Chemo-naïve patients with metastatic gastric cancer were enrolled to receive 4 cycles of TCF-dd (docetaxel initially 85 mg/m2 and cisplatin initially 75 mg/m2 on day 1 [later modified due to toxicity: 70 and 60 mg/m2 respectively], l-folinic acid 100 mg/m 2 on days 1 and 2, 5-fluorouracil 400 mg/m2 bolus and then 600 mg/m2 as a 22 h continuous infusion on day 1 and 2, every 14 days). Subsequently, patients with CR, PR or SD received 4 cycles of COFFI (oxaliplatin 85 mg/m2, irinotecan 140 mg/m2, l-folinic acid 200 mg/m2, 5-fluorouracil bolus 400 mg/m2 on day 1 followed by 2,400 mg/m2 as a 48 h continuous infusion, every 14 days). In both regimens pegfilgrastim 6 mg subcutaneously on day 3 was included. Results: Forty consecutive patients were enrolled. TCF-dd regimen achieved an ORR of 55% (95% CI, 40-70). Twenty-three patients proceeded to COFFI. After this regimen the ORR was then increased to 60% (95% CI, 45-75). Among the 21 patients treated with TCF-dd after the protocol amendments, main grade 3-4 toxicities were: neutropenia (29%), thrombocytopenia (19%), asthenia (24%) and diarrhea (14%). COFFI caused grade 3-4 neutropenia (all not febrile) and diarrhea in 35% and 17% of patients respectively. Conclusions: A sequential strategy with TCF-dd followed by COFFI is very active and may be of special interest in selected patients. © 2010 Springer-Verlag.
PubMed | Papa Giovanni XXIII Hospital, University of Verona, General Hospital, San Vincenzo Hospital and 21 more.
Type: Journal Article | Journal: Future oncology (London, England) | Year: 2016
To assess clinical outcomes in octogenarians treated with docetaxel (DOC) for metastatic castration-resistant prostate cancer.The multicenter retrospective study was based on a review of the pre- and post-DOC clinical history, DOC treatment and outcomes.We reviewed the records of 123 patients (median age: 82 years) who received DOC every 3 weeks or weekly, without significant grade 3-4 toxicities. Median progression-free survival was 7 months; median overall survival from the start of DOC was 20 months, but post-progression treatments significantly prolonged overall survival.The findings of this study suggest that toxicity is acceptable, survival is independent of patients age and survival can be significantly prolonged by the use of new agents.
Passalacqua R.,Concordia Medical |
Annunziata M.A.,Italian National Cancer Institute |
Borreani C.,Fondazione IRCCS Instituto Nazionale dei Tumori |
Diodati F.,University of Parma |
And 4 more authors.
Supportive Care in Cancer | Year: 2016
Purpose: This study examines the development and feasibility of a quality improvement strategy for the translation of evidence-based psychosocial care into clinical practice. Methods: The project involved all staff (oncologists, psychologists, and nurses) of the participating centers. Recommendations concerned: improvement of clinician communication skills; use of a patient question prompt list; assignment of a specialist nurse to each patient; screening for psychological distress and social needs; opportunity to attend a Point of Information and Support. The implementation strategy hinged on context analysis and problem solving. Four to six visits were held in each center by the project team to assist staff in identifying obstacles, finding solutions, and strengthening motivation. The primary variable was the adherence percentage to the recommendations (proportion of subjects receiving each intervention). The number of centers that failed to reach the objective was also reported (adherence percentage <75 %). Results: Twenty-seven of twenty-eight centers completed the study. Lack of resources was the most commonly perceived barrier preimplementation. Five-hundred-forty-five clinicians were actively involved in the project and completed training. The adherence percentage for each recommendation was greater than 85 % except for the question prompt list (78 %; 95 % CI, 73–83 %), where seven centers did not reach the objective. Conclusions: Our findings demonstrate that evidence-based interventions to improve the psychosocial care of people with cancer can be implemented in a diverse range of oncology wards. This requires the involvement and motivation of the entire staff of the ward, support by an expert team, and promotion by policymakers. © 2015, Springer-Verlag Berlin Heidelberg.
PubMed | Santa Maria Nuova Hospital, Concordia Medical, Medical Oncology Unit, Pathology Unit and 2 more.
Type: Journal Article | Journal: Future oncology (London, England) | Year: 2015
To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC).Notch activation was evaluated by immunohistochemistry (IHC) on 65 CRC enrolled within randomized clinical trials assessing first-line bevacizumab-based chemotherapy and on 21 CRC treated with chemotherapy alone.Strong Notch (IHC 3+) activation was negatively associated with response (18 vs 62% in low Notch cases [IHC 0, 1, 2+]; p = 0.016), progression-free survival (4.9 vs 12.1 months; p = 0.002) and overall survival (19.3 vs 30.4 months; p = 0.039). No correlation was found between Notch activation and clinical outcome in CRC treated with chemotherapy alone.A potential role of Notch activation in the antitumor activity of bevacizumab could be hypothesized.
PubMed | Felice Lotti Hospital, Concordia Medical, Unit of Colorectal Surgery, Unit of Medical Oncology and 6 more.
Type: | Journal: European journal of cancer (Oxford, England : 1990) | Year: 2016
Secondary resection is a chance of cure for a subgroup of metastatic colorectal cancer (mCRC) patients with unresectable liver-limited disease. Medical treatment has a dual goal: to induce tumour shrinkage and to prevent disease relapse. The aims of the present analysis were to assess the efficacy of FOLFOXIRI plus bevacizumab in this setting, and to investigate whether this regimen could revert the poor prognosis of high-risk patients defined by clinical and molecular factors. We performed a pooled analysis of patients with unresectable and liver-limited mCRC, treated with first-line FOLFOXIRI plus bevacizumab in three prospective clinical trials by Gruppo Oncologico del Nord Ovest. 205 (37.9%) patients with liver-limited disease were selected, out of 541 treated patients. Liver metastases were synchronous, 4 and bilobar in 90%, 61%, and 79% of cases, respectively. The largest diameter was >5cm in 42% of cases, and 6 segments were involved in 25%. Seventy-four patients (36.1%) underwent R0 or R1 resection of metastases. R2 resections were performed in 17 cases (8.3%). Having <6 involved segments (p<0.001)and achieving RECIST response (p=0.019) were associated with higher chances of resection. R0/R1 resected patients had significantly longer median progression-free survival (PFS) (18.1 versus 10.7 months, HR: 0.48 [0.35-0.66], p<0.001) and overall survival (OS) (44.3 versus 24.4 months, HR: 0.32 [0.22-0.48], p<0.001) compared with other patients, both in the univariate and multivariate analyses (PFS p=0.025; OS p<0.001). The 5-year PFS and OS rate in R0 resected patients were 12% and 43%, respectively. Neither negative baseline characteristicsnor high clinical risk scoresor RAS/BRAF mutations were associated with poor post-resection outcomes. In conclusion, FOLFOXIRI plus bevacizumab demonstrates efficacy in the conversion settingwith considerable long-term outcome resultsindependentof clinical and molecular prognostic factors (NCT00719797, NCT01163396 and NCT02271464).
Gui L.,Yale University |
Zhao L.,Yale University |
Spencer R.W.,Concordia Medical |
Burghouwt A.,Concordia Medical |
And 3 more authors.
Tissue Engineering - Part A | Year: 2011
Functional connective tissues have been developed using tissue engineering approach by seeding cells on biodegradable scaffolds such as polyglycolic acid (PGA). However, a major drawback of tissue engineering approaches that utilize synthetic polymers is the persistence of polymer remnants in engineered tissues at the end of culture. Such polymer fragments may significantly degrade tissue mechanics and stimulate local inflammatory responses in vivo. In this study, several polymeric materials with a range of degradation profiles were developed and evaluated for their potential applications in construction of collagen matrix-rich tissues, particularly tissue-engineered blood vessels. The degradation characteristics of these polymers were compared as were their characteristics vis-à-vis cell adhesion and proliferation, collagen synthesis, and ability to support growth of engineered vessels. Under aqueous conditions at 37°C, Polymer I (comprising 84% glycolide and 16% trimethylene carbonate [TMC]) had a similar degradation profile to PGA, Polymer II (comprising 84% glycolide, 14% TMC, and 2% polyethylene succinate) degradedly more slowly, but Polymer III (comprising 87% glycolide, 7% TMC, and 6% polyethylene glycol) had a more extensive degradation as compared to PGA. All polymers supported cell proliferation, but Polymer III improved collagen production and engineered vessel mechanics as compared with PGA. In addition, more slowly degrading polymers were associated with poorer final vessel mechanics. These results suggest that polymers that degrade more quickly during tissue culture actually result in improved engineered tissue mechanics, by virtue of decreased disruption of collagenous extracellular matrix. © 2011 Mary Ann Liebert, Inc.
Tomasello G.,Concordia Medical |
Liguigli W.,Concordia Medical |
Poli R.,Concordia Medical |
Lazzarelli S.,Concordia Medical |
And 8 more authors.
Gastric Cancer | Year: 2014
Background: We previously studied a dose-dense TCF (TCF-dd) regimen demonstrating its feasibility and an activity comparable to epirubicin-based chemotherapy and TCF q3w in terms of overall survival and time to progression (TTP). We report here the final results of a phase II study of chemotherapy with a modified TCF-dd regimen in locally advanced or metastatic gastric cancer (MGC).Methods and study design: Patients with histologically confirmed measurable MGC, not previously treated for advanced disease, received docetaxel 70 mg/m2day 1, cisplatin 60 mg/m2day 1, l-folinic acid 100 mg/m2days 1 and 2, followed by 5-fluorouracil (5-FU) 400 mg/m2bolus days 1 and 2, and then 600 mg/m2as a 22-h continuous infusion days 1 and 2, every 14 days, plus pegfilgrastim 6 mg on day 3. Patients aged ≥65 years received the same schedule with a dose reduction of 30 %.Results: Study duration: December 2007–November 2010. Forty-six consecutive patients were enrolled (78 % male, 22 % female; median age, 66 years, range, 38–76 years; ECOG PS: 0, 48 %, 1, 46 %). Primary endpoint was overall response rate (ORR). A median of four cycles (range, one to six) was administered. Forty-three patients were evaluated for response (93.5 %) and all for toxicity: 3 complete response (CR), 25 partial response (PR), 10 stable disease (SD), and 5 progressive disease (PD) were observed, for an ORR by intention to treat (ITT) of 61 % (95 % CI 47–75). Median overall survival (OS) was 17.63 months (95 % CI, 13.67–20.67); median progression-free survival was 8.9 months (95 % CI, 6.5–13.4). Twenty-one patients (46.0 %) were treated at full doses without any delay, thus respecting the dose-dense criterion. Most frequent grade 3–4 toxicities were neutropenia (20 %), leukopenia (4 %), thrombocytopenia (2 %), anemia (2 %), febrile neutropenia (6 %), asthenia (22 %), diarrhea (4 %), nausea/vomiting (11 %), and hypokalemia (6 %). Overall, TCF-dd was shown to be safe.Conclusions: The TCF-dd regimen in locally advanced or MGC is confirmed to be feasible and very active and needs to be further tested in randomized studies. © 2013, The International Gastric Cancer Association and The Japanese Gastric Cancer Association.