A Search for Predictive Factors for Hypersensitivity Reactions to Paclitaxel and Platinum Salts in Chemotherapy for Gynecologic Pelvic Neoplasms

Abstract

Aims: To investigate the frequency of and predictive factors for hypersensitivity reactions (HR) to taxanes and platinum salts in a cohort of patients treated for pelvic gynecologic malignancies. Methods: The medical records of all patients with gynecologic pelvic neoplasms treated with chemotherapy at the Department of Gynecologic Oncology, AO Mauriziano Umberto I of Turin, from September 2007 through August 2008, were retrospectively reviewed. Two multivariate models, regarding carboplatin and taxane chemotherapy, respectively, were performed to evaluate the potential predictive value of various clinical features. Results: The incidence of HR was 14% (22/157). Multivariate models showed that menopausal women had a significantly lower probability of HR (OR 0.12, CI 0.02–1.13, p = 0.06 for the carboplatin model and OR 0.05, CI 0.01–0.63, p = 0.02 for the taxane model) while a history of systemic hypersensitivity was associated with a higher but non-significant risk of HR (OR 2.64, CI 0.78–8.95, p = 0.11, for the carboplatin model and OR 3.42, CI 0.94–12.45, p = 0.06, for the taxane model). Conclusion: We confirmed a history of hypersensitivity as a risk factor for HR. Other larger cohorts should be analyzed: we need to find new predictive factors in order to select women who should be submitted to experimental prophylactic strategies.

Dermatological adverse events with taxane chemotherapy

“…With both paclitaxel and docetaxel, the onset is usually very rapid, and seen within a few minutes of starting the infusion [16–18]. The incidence is around 30% without premedication for both agents [1, 17–19], and seems to be on the rise based on recent years [18]. The reaction is generally observed during the first or second cycle of treatment [1, 16–18, 20, 21], and is most often moderate in severity, but severe anaphylactoid manifestations are possible [18, 19, 22].…”

“…The underlying mechanism is poorly understood and does not appear to be IgE-mediated, however, the symptomatology is similar to those of a type I hypersensitivity reaction [17–19, 23]. While the solvent for paclitaxel (Cremophor EL ® , castor oil vehicle) may play a crucial role in these hypersensitivity reactions [1, 3, 5], the solvent for docetaxel (Tween 80, polyoxyethylene-20-sorbitan monooleate) is less frequently incriminated [3].…”

A cohort study of hypersensitivity reaction in patients with epithelial ovarian cancer treated with carboplatin

“…A few risk factors for platinum-based hypersensitivity reaction have been described by different studies, including the number of chemotherapy cycles,6 a pre-menopausal state,7 an allergic history to drugs or environmental stimulation,8 9 a maximum dose of carboplatin ≥650 mg, 10 and a long platinum-free interval 9–11. The association between the dosage of drugs and the risk of hypersensitivity reaction has been confirmed in cohort studies 12.…”

Feasibility of withholding dexamethasone premedication for hypersensitivity reactions associated with paclitaxel administration

“…Although all practical strategies were applied in this study, grade III HSR occurred in approximately 40% of patients. Several risk factors, such as menopausal status, high BMI, history of hypersensitivity, and respiratory dysfunction, are recognized to predict the incidence of paclitaxel HSR in a subgroup of patients with gynecological cancers [1,8]. Sendo et al reported 4 risk factors associated with HSR: history of mild dermal reactions in previous courses, presence of respiratory dysfunction, body mass index >25, and postmenopausal status at the time of ovariectomy.…”

“…These authors concluded that the marked depletion of estrogen may be related to a change in sensitivity to paclitaxel by affecting vascular endothelial function, resulting in the enhancement of the HSR to paclitaxel [1]. Conversely, Piovano et al reported that postmenopausal women showed a protective effect for HSR, but a history of systemic hypersensitivity was associated with higher HSR [8]. Like Piovano et al, we found an insignificantly higher proportion of women with premenopausal status in the group with HSR than in the group with no HSR (50% vs 23%, P = 0.15).…”