Observational Study of Clinical Practice in Patients with Pancreatic Adenocarcinoma in Greece.

BACKGROUND: During the last decade, significant improvement was made in systemic therapy of pancreatic adenocarcinoma (PAC). The impact of this progress in everyday clinical practice has not been fully described yet. The aim of the study was to investigate the pattern followed by Greek Medical Oncologists regarding the treatment of patients with PAC. METHODS: This observational, noninterventional multicenter study recorded clinical data from the files of 200 active patients (alive and under treatment or follow-up) for a two-year period (November 2015 until November 2017) from 20 oncology centers around Greece. RESULTS: In total, 51 (25.5%) patients underwent radical surgical resection of PAC, and 40 (78.4%) of them received adjuvant and 1 (2.0%) neoadjuvant chemotherapy. The median time to recurrence was 7.9 months, and median overall survival (OS), 20.2 months. First-line chemotherapy was administered to 193 (96.5%) patients. The majority of patients were treated with the combination of nab-paclitaxel-gemcitabine (NPG), 5-fluorouracil, leucovorin, irinotecan, oxaliplatin (FOLFIRINOX), or gemcitabine monotherapy. Of them, 39.5% responded to the treatment. Median OS and PFS were 14.1 months and 7.0 months, respectively. Second-line treatment was administered to 112 patients. The majority received NPG, FOLFIRINOX/capecitabine, oxaliplatin, irinotecan (CAPOXIRI), or 5-fluorouracil, leucovorin, oxaliplatin (FOLFOX)/capecitabine, oxaliplatin (CAPOX). Median OS with second-line treatment was 8.6 months, and median PFS, 5.5 months. The most common chemotherapy sequences were NPG as first-line followed by FOLFIRINOX/CAPOXIRI as second-line, NPG followed by FOLFOX/CAPOX, NPG followed by other regimens, and FOLFIRINOX/CAPOXIRI followed by NPG. CONCLUSION: This study described the significant improvement in prognosis of PAC patients receiving palliative chemotherapy and the relatively high rate of receipt of second-line chemotherapy, according to real-world data. However, due to the nonrandomized nature of the study, any comparison between different chemotherapy regimens should be regarded with caution.

Neoadjuvant sequential epirubicin and docetaxel followed by surgery-radiotherapy and post-operative docetaxel or gemcitabine/vinorelbine combination based on primary response: a multimodality approach for locally advanced breast cancer.

BACKGROUND: Locally advanced breast cancer (LABC) remains a major clinical issue despite progress achieved in recent years. Herein, we present the mature results of a multimodality treatment program tailoring epirubicin (EPI), docetaxel (DOC) and gemcitabine-vinorelbine (GEV) peri-operatively in LABC. PATIENTS AND METHODS: Stage III, Eastern Cooperative Oncology Group-Performance status ≤2 patients were eligible. A biopsy documentation had to be performed before the start of chemotherapy (CT). Treatment consisted of four EPI (100 mg/m(2), d1q2w) followed by three DOC (100 mg/m(2), d1q3w); surgery 3-4 weeks from CT completion, followed by radiation therapy (RT) and CT according to response; partial or complete (PR/CR):DOC, no change or progressive disease (NC/PD):GEV. Primary endpoints were: (a) response and conversion to operability/conservative surgery and (b) overall survival (OS) and time to recurrence (TTR). RESULTS: Fifty-six women, aged 32-75 (median 52 years), 24 IIIA and 32 IIIB were enrolled; 53 patients completed the entire program. Toxicity was acceptable and no treatment-related death was observed. EFFICACY: clinical response rate (RR) 71.4% (40 patients); clinical complete response rate 33.9% (19 patients). Pathological response rate (RR) 67.8% (38 patients); pathological complete response rate 21.4% (12 patients). 33 (58.9%) and 19 (33.9%) patients, respectively, had radical and conservative operations without increased morbidity. After a median follow-up of 62 months, median OS has not yet been reached, while median TTR was 42 months. OS was longer in patients with clinical (p = 0.004) and pathological response (p = 0.002), RT (p < 0.0001) and post-operative DOC (p = 0.038). TTR was favorably affected by pR (p < 0.0001), RT (p < 0.0004) and post-operative DOC (p = 0.005). Pre-operative CT seemed to be equally active throughout all subgroups according to histology, ER/PR and HER2 status. CONCLUSION: The treatment program of the present study allowed for the completion of an effective therapy at the cost of acceptable toxicity. The results of this study suggest a central role of CT for LABC and the value of eventually dose-dense, EPI- and DOC-based CT in a large proportion of LABC patients, regardless of biological tumor profile. Furthermore, tumor response (cR, pR) is an important surrogate for patients survival and further therapy management.

A phase I trial of adoptive transfer of allogeneic natural killer cells in patients with advanced non-small cell lung cancer.

HLA-mismatched natural killer (NK) cells have shown efficacy in acute myeloid leukemia, and their adoptive transfer in patients with other malignancies has been proven safe. This phase I clinical trial was designed to evaluate safety (primary endpoint) and possible clinical efficacy (secondary endpoint) of repetitive administrations of allogeneic, in vitro activated and expanded NK cells along with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Patients with unresectable, locally advanced/metastatic NSCLC receiving 1st/2nd line chemotherapy were eligible to receive 2-4 doses of activated NK cells from two relative donors. Donor's CD56(+) cells were cultured for 20-23 days with interleukin-15 (IL-15) and hydrocortisone (HC) and administered intravenously between chemotherapy cycles. Premedication with corticosteroids and/or H1 inhibitors was allowed. Sixteen patients (performance status 0-1) with adenocarcinoma (n = 13) or squamous cell carcinoma (n = 3) at stage IIIb (n = 5) or IV (n = 11) receiving 1st (n = 13) or 2nd (n = 3) line treatment were enrolled. Fifteen patients received 2-4 doses of allogeneic activated NK cells (0.2-29 × 10(6)/kg/dose, median 4.15 × 10(6)/kg/dose). No side effects (local or systemic) were observed. At a median 22-month follow-up (range, 16.5-26 months) 2 patients with partial response and 6 patients with disease stabilization were recorded. Median progression free survival and overall survival were 5.5 and 15 months, respectively. A 56% 1-year survival and a 19% 2-year survival were recorded. In conclusion, repetitive infusions of allogeneic, in vitro activated and expanded with IL-15/HC NK cells, in combination with chemotherapy are safe and potentially clinically effective.

Bevacizumab combined with two-weekly paclitaxel as first-line therapy for metastatic breast cancer.

BACKGROUND: Metastatic breast cancer remains a major clinical issue despite progress achieved in recent years. Three randomised trials have demonstrated the benefit of combining bevacizumab with various taxane schedules. Herein, this study sought to investigate an alternative bevacizumab-taxane regimen as first-line treatment for metastatic breast cancer. PATIENTS AND METHODS: Patients with metastatic breast cancer and who received first-line bevacizumab 10 mg/kg with paclitaxel 135 mg/m(2) every 2 weeks were studied. RESULTS: All 43 enrolled patients were evaluable for efficacy and safety. The response rate was 58%; a further 40% achieved stable disease. After a median follow-up of 16 months, disease had progressed in 9 patients (21%). Treatment was well tolerated: grade 4 toxicities were absent; grade 3 adverse events comprised neutropenia (5%; no febrile neutropenia), hypertension (2%) and neuropathy (2%). CONCLUSION: This regimen may provide improved patient acceptability, quality of life and pharmacoeconomic benefits over a weekly paclitaxel schedule, and deserves further evaluation.

Salvage therapy of pretreated advanced breast cancer with bevacizumab and paclitaxel every two weeks: a retrospective case review study.

BACKGROUND: Targeting angiogenesis is nowadays one of the most promising approaches for breast cancer. Bevacizumab (BEV), a VEGF-trap monoclonal antibody, was recently approved in combination with paclitaxel (PAC) for the first line treatment of advanced breast cancer (ABC). The activity of this combination in pretreated patients is not known. METHODS: Patients with pretreated ABC and progressive disease received BEV 10 mg/kg with PAC 135 mg/m(2) every two weeks for six months and then maintenance with BEV 15 mg/kg every three weeks until progression. This regimen was chosen for better patient convenience, while maintaining the same dose intensity for both drugs. RESULTS: 42 patients were reviewed retrospectively (41 f, 1 m, mean age 57 years). Overall response rate was 35.7%. Stable disease was observed in 45.2% of patients, whereas 14.3% of patients progressed. The median overall survival was greater than 20 months, with a one year rate of 83.4%. The median progression free survival was 12.1 months, with a one year rate of 51.8%. Toxicity was in general acceptable. CONCLUSION: This biweekly BEV/PAC combination seems to be active with acceptable toxicity in pretreated ABC with an advantage over the weekly regimen regarding quality of life and preservation of resources.

Paraneoplastic cerebellar degeneration in a patient with pseudomyxoma peritonei and breast cancer: case report and literature review.

The case of a 31-year-old woman with progressive cerebellar degeneration preceding by several months the diagnosis and treatment of breast cancer initially and pseudomyxoma peritonei (PMP) with evidence of causative association with the latter is presented. Despite various chemotherapeutic and surgical manipulations, the patient did not substantially improve and succumbed 20 months following initial diagnosis of the neurological disorder. Interestingly, neurological symptoms partially regressed transiently only after surgical debulking of the PMP and not after the remission of breast cancer after various chemotherapeutic regimens suggesting an etiological relationship of the former and the cerebellar degeneration. Early recognition and appropriate therapy of this rare complication of PMP is imperative as it may be crucial for the outcome.

Biweekly gemcitabine (GEM) in combination with erlotinib (ERL): an active and convenient regimen for advanced pancreatic cancer.

BACKGROUND: Pancreatic cancer remains a disease of high mortality and one of the most frustrating, resistant solid neoplasms to treat. The aim of this study was to evaluate a biweekly gemcitabine plus daily erlotinib regimen in patients with advanced (stage III-IV) pancreatic cancer in terms of overall survival and time to progression of the disease. The secondary aim was to record treatment related toxicities. PATIENTS AND METHODS: Twenty-seven patients with metastatic non-operable pancreatic adenocarcinoma, stage III-IV, consented to receive chemotherapy with gemcitabine and erlotinib. Patients received first-line treatment with gemcitabine (2 g/m(2) via 90 min i.v. infusion every two weeks) and 100 mg erlotinib per os every day, for at least 12 consecutive courses (6 cycles). Treatment was discontinued at disease progression and/or serious toxicity. RESULTS: The objective response rate was 25.9% (95% confidence interval [CI]: 11.1-46.3%) and the stable disease rate was 59.3% (95% CI: 38.8-77.6%). The one-year overall survival was 20%. The median overall survival and time to progression at the time of assessment was 7.5 months (95% CI: 3.6-42 months) and 5.5 months (95% CI: 1.5-10 months), respectively. Overall survival and time to progression were related to response (p<0.001), while time to progression was further related to disease stage (p=0.011). No grade 4 haematological or non-haematological toxicities were observed. CONCLUSION: The biweekly regimen of gemcitabine plus erlotinib has similar toxicity and efficacy to weekly administration, presenting both patients and hospital resource departments with a clearly more convenient therapy alternative.

Bevacizumab added to the irinotecan and capecitabine combination for advanced colorectal cancer: a well-tolerated, active and convenient regimen.

OBJECTIVES: The literature data regarding bevacizumab (BEV) administered together with capecitabine (CAP) and irinotecan (IRI) in patients with advanced colorectal cancer (CRC) are limited. The safety and efficacy of the addition of BEV to the IRI and CAP (XELIRI) regimen were retrospectively analyzed and reported. PATIENTS AND METHODS: Adult patients 18 years or older with advanced CRC, Eastern Cooperative Oncology Group performance status (ECOG PS) < or =2, exposed to < or =1 chemotherapy (CT) regimen not including IRI or CAP, received BEV 7.5 mg/kg and IRI 220 mg/m2 both on day 1; CAP 1.8 g/m2/d, dl-14. The treatment was repeated every 21 days up to a total of 8 cycles. Responding or stabilized patients were treated with BEV 7.5 mg/m2, administered as maintenance every 21 days until disease progression. RESULTS: Thirty-four patients were treated, the majority (29, 85.3%) in first-line: eighteen (53%) male, 16 (47%) female, and aged 37-83 years (median 69.5). The treatment was moderately tolerated with mainly gastrointestinal complications: hematological, cardiovascular and other toxicities were also recorded, but they were manageable. No treatment-related death was noted. The overall response rate (RR) was 47.1%, while 41.2% of the patients achieved stable disease. Median progression-free survival and overall survival were 8 and 14 months, respectively, with 16% progression-free and 62% alive at 12 months. CONCLUSION: BEV-XELIRI is effective and well tolerated, leading to disease control in a vast majority of patients with advanced CRC.