Oral Capecitabine-Vinorelbine is Associated with Longer Overall Survival When Compared to Single-Agent Capecitabine in Patients with Hormone Receptor-Positive Advanced Breast Cancer.

Background: Single-agent capecitabine (C) is a moderately effective chemotherapeutic compound in the treatment of patients with HER2-negative metastatic breast cancer (mBC). The capecitabine-vinorelbine (CV) combination is also used due to a good tolerability profile, but no studies have demonstrated its superiority over single-agent C. Methods: We conducted a retrospective analysis to compare overall response rate (ORR), progression-free survival (PFS), overall survival (OS) and incidence of adverse events (AEs) in patients with HER2-negative mBC treated with CV vs. single-agent C. Results: Out of 290 patients included in this study, 127 (43.8%) received single-agent C, while 163 (56.2%) patients were treated with CV. Median PFS was similar in patients treated with single-agent C or CV, while CV was associated with significantly longer OS in patients with hormone receptor-positive (HR+) BC. This OS advantage was confirmed at multivariable analysis also after propensity score-based matching of patients according to relevant clinical or tumor characteristics. When compared with single-agent C, CV was associated with higher incidence of G3/G4 and any-grade nausea/vomiting, diarrhea and increased transaminases. Conclusions: While prospective studies are needed to confirm our findings, the potential OS advantage of CV over single-agent C in HR+ mBC patients must be weighed against a significantly higher incidence of AEs.

Antitumor activity and safety profile of weekly carboplatin plus paclitaxel in metastatic breast cancer: a ten-year, monocentric, retrospective study.

BACKGROUND: Taxanes are a mainstay in the treatment of metastatic breast cancer (mBC). Combination chemotherapy, including platinum-taxens doublets, can improve tumor responses and progression-free survival (PFS), but is associated with more toxicities and an uncertain benefit in terms of overall survival (OS). METHODS: We performed a retrospective study on 274 consecutive patients with mBC treated at the Division of Medical Oncology of Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, during the decade 2007-2016 with the combination of carboplatin AUC 2 plus paclitaxel 80 mg/m2, both given on days 1 and 8 in every 21-day cycle. RESULTS: 264 patients were evaluable for treatment safety and activity. The objective response rate (ORR) was 44.7%. Median PFS and OS were 8.6 and 23.7 months, respectively. Triple-negative breast cancer (TNBC) patients had significantly lower PFS and OS times compared to other biology groups. At multivariable analysis, previous exposure to taxanes, HR-positive HER2-negative biology, a higher number of metastatic sites, and de novo metastatic disease at diagnosis were associated with reduced PFS, while receiving maintenance therapy correlated with improved PFS. Overall, the treatment was quite well tolerated, with 10.2% of patients discontinuing one or both drugs because of adverse events (AEs). G3-G4 neutropenia occurred in 16.8% of patients, while the incidence of febrile neutropenia was 2.3%. CONCLUSIONS: Weekly carboplatin-paclitaxel regimen is active and well tolerated in mBC treatment. Prospective studies should be conducted to compare its efficacy and tolerability with standard single-agent paclitaxel or docetaxel treatment schedules, as well as with more recent combination regimens.

Cytotoxic extravasation: an issue disappearing or a problem without solution?

PURPOSE: The incidence and management of antitumoral compound extravasation that occurred in our medical day hospital unit were registered in a 10-year period. METHODS: A total of 114 episodes were consecutively recorded out of an estimated number of 211,948 administrations performed (0.05%). Type of compound, localization, timing, symptoms, treatment, resolution, or sequelae were documented. RESULTS: Extravasations after anthracyclines (17/114), platinum compounds (34/114), vinca alkaloids (7/114), and taxanes (34/114) were more frequently associated with edema and erythema ± pain. Five cases of monoclonal antibodies extravasation were observed without sequelae. With the involvement of an interdisciplinary task force and the use of dedicated guidelines, conservative management was successful in all patients. In the great majority of cases, recovery was complete within 48 hours after antidote administration. The support of our pharmacy was crucial. Physiatric evaluation was considered in several cases. No patients required surgery. CONCLUSIONS: We confirm that the adopted standardized approach to this event resulted in a satisfactory outcome and could be suggested as appropriate for managing extravasation in a large clinical context.

Are antineoplastic drug acute hypersensitive reactions a submerged or an emergent problem? Experience of the Medical Day Hospital of the Fondazione IRCCS Istituto Nazionale Tumori.

BACKGROUND: Acute hypersensitivity reactions are adverse events potentially associated with antineoplastic drug infusions. Their occurrence can be particularly relevant in an outpatient environment where time of administration and subsequent observation is limited to a short period of time. In addition, concern about the onset of more severe hypersensitivity reactions can limit subsequent use of crucial drugs. METHODS: During a 3-year observational period, we collected a total of 240 infusional acute hypersensitivity reactions out of 56,120 administrations performed, with an overall incidence of 0.4%. RESULTS: In order of frequency, platinum derivatives, taxanes and monoclonal antibodies accounted for the highest incidences. Their relative frequency was: oxaliplatin, 2.5%; carboplatin, 0.4%; paclitaxel, 1.2%; docetaxel, 1.2%; trastuzumab, 1.2%, and rituximab, 1.2%. CONCLUSIONS: Since the number of chemotherapeutic agents is steadily increasing, much attention should be paid to such reactions, particularly when several administrations are performed daily, and where management of the potential risk associated with specific drugs is mandatory. Their occurrence represents an unpredictable, unexpected and often hard to manage contingency, and our opinion is that observation and consciousness of this issue are fundamental for its appropriate management. We describe our experience, emphasizing the role of this toxicity and explaining how this awareness allowed us to define some empirical rules to handle acute hypersensitivity reactions.