Based on observations of a discrepancy between 'hypersensitivity' reactions to docetaxel (DT) and the clinical features of allergic reactions, we explored the hypothesis that DT-induced acute hypersensitivity reactions (AHRs) have a non-allergic origin. Forty cancer patients receiving DT and 16 patients receiving other potentially allergenic chemotherapeutic agents were included in the study. All DT patients received standard pre- and post-medication. Before, during and after administration of the drugs, clinical symptoms and signs were recorded, and serial blood sampling was performed for the first 2 cycles for all patients or in all subsequent cycles in case of AHRs. Plasma histamine and serum tryptase, two established drug allergy markers, were measured. Seventy-five chemotherapy sessions were evaluable. Nine patients on DT, two on paclitaxel (PT) and one on pegylated doxorubicin experienced an AHR during the first course of chemotherapy. In all cases, heart rate remained stable or increased, while arterial pressure was unchanged or raised; no hypotension or bradycardia was noted. All episodes resolved with discontinuation of drug and did not reappear during a re-challenge with the same agent 30 min later. Tryptase levels were normal in all pre- and post-exposure samples (post-exposure: 11.32+/-35.63 microg/l, normal values <13.5 microg/l). In all but one AHR-free PT, pre- and post-exposure histamine concentrations remained normal (post-exposure: 2.86+/-11.88 nM, normal values <10 nM). No eosinophilia or basophilia was observed. We conclude that 'hypersensitivity' reactions to DT seem not to be histamine or tryptase mediated; thus, their allergenic nature should be questioned. The underlying mechanism may be related to other biological processes such as the release of vasoactive molecules or non-histamine/tryptase-mediated allergy. If the former is demonstrated by further study, the safety of DT administration will be confirmed, and the pre- and post-medication practice might be revisited.
Objectives: To evaluate the efficacy and safety of docetaxel in combination with carboplatin as salvage treatment in women with metastatic breast cancer (MBC). Patients and Methods: Chemotherapy-pretreated women with MBC were treated with docetaxel 75 mg/m2 as 1-hour i.v. infusion followed by carboplatin AUC 6 mg/ml·min, using the Calvert’s formula, as 30-min i.v. infusion. Cycles were repeated on an outpatient basis every 3 weeks. Results: Thirty-six patients received a total of 210 chemotherapy cycles (median 6 cycles/patient). All but one patient had previously received anthracyclines for the treatment of metastatic disease and half of the patients had failed to respond to front-line treatment. Twenty-eight (78%) patients had visceral disease. On an intention-to-treat analysis there were three (8%) complete and 19 (53%) partial responses for an overall response rate of 61% (95% CI: 45.2–77.0%). The response rate was 44% (2 CRs, 6 PRs) among 18 patients who had progressive or stable disease as best response to front-line treatment. The median duration of response was 8 months, the median time to tumor progression 10 months, and the probability of 1-year survival 66%. Grade 3–4 neutropenia was the main hematologic toxicity occurring in 16 (45%) patients or 36 (17%) cycles. Seven (19%) patients developed 8 (4%) febrile neutropenic episodes. Grade 3 thrombocytopenia occurred in 4 (11%) patients or 6 (3%) cycles. Non-hematologic toxicity was generally mild. G-CSF was used in 19 (53%) patients or 134 (64%) cycles. There was one sudden death possibly related to the treatment. Conclusion: The docetaxel-carboplatin combination is an active outpatient salvage regimen for the treatment of women with MBC relapsing or not responding to anthracycline-based front-line therapy.
This paper reports the case of a 45-year-old female with histologically documented, multiple cutaneous metastases in the palmar and plantar surface of the fingers and toes originating from a breast adenocarcinoma after treatment with a docetaxel and pegylated liposomal doxorubicin regimen. The rarity of such a metastatic pattern from breast cancer and the eventual association with the chemotherapy administered are thoroughly discussed.
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