Hypersensitivity Reactions in Ovarian Cancer Patients Receiving Paclitaxel

Cormio, Gennaro; Vagno, Giovanni Di; Ga, Melilli; Cazzolla, Angela Pia; Gesu, Giuseppe Di; Carriero, Carmine; Cramarossa, D; Loverro, Giuseppe; Selvaggi, Luigi

doi:10.1179/joc.1999.11.5.407

Cited by 23 publications

(10 citation statements)

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“…It has been reported that the incidence rate of paclitaxel-induced HSRs is 8-14% in patients with ovarian cancer. 2,3,17,18 Consistent with these data, the incidence of grade 2 HSRs to paclitaxel observed in the present study was 11.9%, which was also comparable to those reported in our previous study, 5 in which 14 (13.3%) of 105 patients with ovarian cancer who undertook postoperative paclitaxel and carboplatin combination chemotherapy showed grade 2 HSRs, regardless of the presence of premedication with glucocorticoid, and histamine H 1 and H 2 antagonists. However, it is noteworthy that no signs of HSRs were observed after paclitaxel infusion, when pretreated with pemirolast in combination with the conventional premedication regimen.…”

Section: Discussionsupporting

confidence: 81%

“…However, the use of paclitaxel is sometimes limited due to the incidence of severe hypersensitivity reactions (HSRs). The HSRs to paclitaxel are characterized by flushing, chest discomfort, respiratory distress and pulmonary edema, [1][2][3][4] and the incidence is particularly high in patients with ovarian cancer who undertook postoperative chemotherapy containing paclitaxel. 5 To avoid the HSRs, premedication containing histamine H 1 and H 2 antagonists in combination with glucocorticoids is always prescribed, [6][7][8][9][10] although the preventive effect is by no means complete.…”

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confidence: 99%

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Prophylactic effect of pemirolast, an antiallergic agent, against hypersensitivity reactions to paclitaxel in patients with ovarian cancer

Yahata

Saito

Sendo

et al. 2006

Intl Journal of Cancer

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We have previously shown that sensory nerve peptides contribute to the pathogenesis of pulmonary hypersensitivity reactions (HSRs) to paclitaxel in rats. Moreover, pemirolast, an antiallergic agent, reverses the HSRs to paclitaxel, although the mechanism is considered to result from the blockade of paclitaxel-induced release of sensory peptides, rather than the inhibition of histamine release. In the present study, we investigated the preventive effect of pemirolast against acute HSRs in a total of 84 patients who undertook postoperative paclitaxel plus carboplatin chemotherapy every 4 weeks for ovarian cancer. Patients were assigned to receive oral lactose (placebo) or pemirolast (10 mg), 2 hr before paclitaxel infusion. All patients received conventional premedication, including oral diphenhydramine, intravenous ranitidine and intravenous dexamethasone, 30 min before paclitaxel infusion. The HSRs that led to the discontinuance of paclitaxel infusion (grade 2) occurred in 5 of 42 patients in placebo group, whereas none of pemirolast-treated 42 patients showed any signs of HSRs. Plasma histamine concentrations were not changed after paclitaxel infusion in either group. Our present findings suggest that pemirolast is potentially useful for prophylaxis of paclitaxelinduced HSRs. In this respect, the use of pemirolast as premedication is expected to be beneficial to the safety management in patients who undergo chemotherapy containing paclitaxel. ' 2005 Wiley-Liss, Inc.Key words: paclitaxel; hypersensitivity reactions; pemirolast; histamine; ovarian cancer Paclitaxel (Taxol) is a widely used chemotherapeutic agent for several malignancies, including ovarian cancer, breast cancer, endometrial cancer, nonsmall-cell lung cancer and stomach cancer. However, the use of paclitaxel is sometimes limited due to the incidence of severe hypersensitivity reactions (HSRs). The HSRs to paclitaxel are characterized by flushing, chest discomfort, respiratory distress and pulmonary edema, 1-4 and the incidence is particularly high in patients with ovarian cancer who undertook postoperative chemotherapy containing paclitaxel. 5 To avoid the HSRs, premedication containing histamine H 1 and H 2 antagonists in combination with glucocorticoids is always prescribed, [6][7][8][9][10] although the preventive effect is by no means complete. However, there has been no direct evidence suggesting that the HSRs to paclitaxel are mediated by the release of histamine from mast cells or basophils. We have recently shown that paclitaxel causes pulmonary vascular hyperpermeability and edema and the decrease in arterial partial oxygen pressure in rats.11 The toxic effects of paclitaxel in rat lungs are attenuated by neurokinin NK 1 and NK 2 receptor antagonists, or chemical sensory denervation with repeated capsaicin treatment, but not by histamine H 1 or H 2 antagonists, thereby suggesting that the pulmonary adverse reactions induced by paclitaxel are mediated by sensory nerve peptides such as substance P and neurokinin A, but not by mast cell hista...

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Section: Discussionsupporting

confidence: 81%

mentioning

confidence: 99%

Prophylactic effect of pemirolast, an antiallergic agent, against hypersensitivity reactions to paclitaxel in patients with ovarian cancer

Yahata

Saito

Sendo

et al. 2006

Intl Journal of Cancer

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“…The life-threatening hypersensitivity of the paclitaxel/Cremophor/EtOH formulation observed in early clinical studies was attributed to Cremophor (30). The hypersensitivity is currently managed by premedication with steroids (31). In addition, as discussed in Introduction, paclitaxel is entrapped in Cremophor micelles.…”

Section: Discussionmentioning

confidence: 99%

Paclitaxel-Loaded Gelatin Nanoparticles for Intravesical Bladder Cancer Therapy

Lu¹,

Yeh²,

Tsai³

et al. 2004

Clinical Cancer Research

220

107

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Purpose: The present report describes the development of paclitaxel-loaded gelatin nanoparticles for use in intravesical therapy of superficial bladder cancer. The commercial formulation of paclitaxel contains Cremophor, which forms micelles and thereby entraps the drug and reduces its partition across the urothelium.Experimental Design: Paclitaxel-loaded gelatin nanoparticles were prepared using the desolvation method, and their physicochemical and biological properties were characterized.Results: The size of the particles ranged from 600 to 1,000 nm and increased with the molecular weight of the gelatin polymer. Under optimal conditions, the yield was >80%, and the drug loading was 0.7%. Wide-angle X-ray diffraction analysis showed that the entrapped paclitaxel was present in an amorphous state, which has higher water solubility compared with the crystalline state. Identical, rapid drug release from nanoparticles was observed in PBS and urine, with ϳ90% released at 37°C after 2 hours. Treatment with a protease (i.e., Pronase) rapidly degraded the nanoparticles, with half-lives of 23.8 minutes, 0.6 minute, and 0.4 minute in the presence of 0.01, 0.05, and 0.25 mg/mL Pronase, respectively. The paclitaxel-loaded nanoparticles were active against human RT4 bladder transitional cancer cells; the IC 50 paclitaxel-equivalent concentrations were nearly identical to those of aqueous solutions of paclitaxel, i.e., ϳ30 nmol/L (equivalent to ϳ25 ng/mL) for 2-hour treatments and ϳ4 nmol/L for 96-hour treatments. In dogs given an intravesical dose of paclitaxel-loaded particles, the drug concentrations in the urothelium and lamina propria tissue layers, where Ta and T1 tumors would be located, were 7.4 ؎ 4.3 g/g (mean ؎ SD; 3 dogs; 9 tissue sections), which were 2.6؋ the concentrations we reported for dogs treated with the Cremophor formulation.Conclusions: Paclitaxel-loaded gelatin nanoparticles represent a rapid release, biologically active paclitaxel formulation that can be used for intravesical bladder cancer therapy.

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“…basal levels). (3 -6); however, the requirement of cremophor as a solvent has important drawbacks, due to its irritating and toxic properties (33,34), that limit the i.p. administrable dose in comparison to the i.v.…”

Section: Resultsmentioning

confidence: 99%

A Paclitaxel-Hyaluronan Bioconjugate Targeting Ovarian Cancer Affords a Potent In vivo Therapeutic Activity

Banzato

Bobisse

Rondina

et al. 2008

Clinical Cancer Research

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Purpose: This study was designed to evaluate the pharmacologic and biological properties of a paclitaxel-hyaluronan bioconjugate (ONCOFID-P) against IGROV-1and OVCAR-3 human ovarian cancer xenografts following i.p. administration. Experimental Design: In vitro tumor sensitivity to ONCOFID-P was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, whereas bioconjugate interaction with cells was studied cytofluorimetrically and by confocal microscopy. In vivo toxicity was assessed by a single-dose maximum-tolerated dose, peripheral blood cell count determination and by histologic analysis. Biodistribution of the compound was evaluated with a small animald edicated scintigraphy gamma camera following injection of 99mTc-labeled ONCOFID-P. Pharmacokinetic analysis was also carried out. Female severe combined immunodeficiency mice implanted with ovarian cancer cells underwent treatment with ONCOFID-P or free paclitaxel starting from day 7 or 14 after tumor injection, and survivals were compared. Results: ONCOFID-P interacted with CD44, entered cells through a receptor-mediated mechanism, and exerted a concentration-dependent inhibitory effect against tumor cell growth. After i.p. administration, the bioconjugate distributed quite uniformly within the peritoneal cavity, was well-tolerated, and was not associated with local histologic toxicity. Pharmacokinetic studies revealed that blood levels of bioconjugate-derived paclitaxel were much higher and persisted longer than those obtained with the unconjugated free drug. Intraperitoneal treatment of tumorbearing mice with the bioconjugate revealed that ONCOFID-P exerted a relevant increase in therapeutic activity compared with free drug. Conclusions: ONCOFID-P significantly improved results obtained with conventional paclitaxel, in terms of in vivo tolerability and therapeutic efficacy; these data strongly support its development for locoregional treatment of ovarian cancer.Ovarian cancer is the most common cause of death from gynecologic malignancy and is the fifth leading cause of cancerrelated death (1). Intravenous administration of taxane-and platinum-based chemotherapy represents the current standard of postoperative care for patients with advanced neoplasia. This therapeutic regimen is also considered for high-risk patients with early stage tumors in an adjuvant setting, to eradicate residual disease following surgical debulking. Despite these approaches having resulted in improved survival over the last decade, nonetheless, relapses still occur in the majority of cases and represent the major problem for patients with advanced disease (2).A potential solution to these obstacles takes into consideration the biological behavior of ovarian cancer, which is mainly confined to the peritoneal cavity for most of its initial natural course. The biology of the tumor offers the possibility of delivering drugs directly within the peritoneum to achieve a theoretical potential for increased exposure of the tumor to the antineoplastic agen...

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Hypersensitivity Reactions in Ovarian Cancer Patients Receiving Paclitaxel

Abstract: Retreatment with the original paclitaxel solution is safe in almost all patients with hypersensitivity reactions. The drug should be administered within the next 24 hours with a new premedication protocol.

Cited by 23 publications

References 5 publications

Prophylactic effect of pemirolast, an antiallergic agent, against hypersensitivity reactions to paclitaxel in patients with ovarian cancer

Prophylactic effect of pemirolast, an antiallergic agent, against hypersensitivity reactions to paclitaxel in patients with ovarian cancer

Paclitaxel-Loaded Gelatin Nanoparticles for Intravesical Bladder Cancer Therapy

A Paclitaxel-Hyaluronan Bioconjugate Targeting Ovarian Cancer Affords a Potent In vivo Therapeutic Activity

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