Prevention of carboplatin-induced hypersensitivity reactions in women with ovarian cancer

Abstract

Background

Carboplatin-based chemotherapy offers high response rates and improved overall survival for women with epithelial ovarian cancer, but its use is limited by the occurrence of hypersensitivity reactions. To evaluate the efficacy of prophylactic diphenhydramine for hypersensitivity reaction prevention, we reviewed the incidence of hypersensitivity reactions and identified patients at high risk of hypersensitivity reactions.

Methods

Women receiving ≥6 cycles of carboplatin-based chemotherapy for epithelial ovarian cancer were identified from our institutional database at the Princess Margaret Cancer Centre. Institutional policy was changed in 2009 to introduce diphenhydramine prophylaxis for patients receiving ≥6 cycles of carboplatin. Additional clinical data were abstracted from the patient record.

Results

Between 2006 and 2012, 450 women received ≥6 cycles of carboplatin-based chemotherapy for epithelial ovarian cancer. Two hundred and ninety-one women received prophylaxis with diphenhydramine. Carboplatin-induced hypersensitivity reactions occurred in 41 of 449 patients (9%). Univariable predictors of carboplatin-induced hypersensitivity reactions included administration of 8 to 10 cycles of carboplatin, history of other drug allergies and a platinum-free interval >12 months. BRCA mutational status was not predictive. In a multivariable analysis, the number of cycles of carboplatin and a platinum-free interval >12 months were independent predictors of hypersensitivity reactions. There was a trend towards diphenhydramine prophylaxis reducing the incidence of hypersensitivity reactions in women with a platinum-free interval compared to continuous delivery; this was most marked when the platinum-free interval was >12 months (n = 64) (OR: 0.2 (95% CI: 0.046–0.83), p = 0.03).

Conclusions

The administration of diphenhydramine to women who have a platinum-free interval may reduce the risk of hypersensitivity reaction, but prospective evaluation is required.

Keywords

Hypersensitivity carboplatin diphenhydramine prevention risk factors

Get full access to this article

View all access options for this article.

References

Kennedy

Dodge

et al.

Follow‐up of patients who are clinically disease‐free after treatment for fallopian tube, primary peritoneal, and epithelial ovarian cancer. Program in Evidence‐Based Care Guideline No.: 4‐22, Toronto, ON: Cancer Care Ontario, 2015. .

Fung MFK, Kennedy E, Francis J, et al.; Members of the Gynecologic Cancer Disease Site Group. Optimal chemotherapy for recurrent ovarian cancer. Program in Evidence-based Care Evidence-Based Series No.: 4-3 Version 3 (in review). Toronto, ON: Cancer Care Ontario, 2011.

Markman

Kennedy

Webster

et al.

Clinical features of hypersensitivity reactions to carboplatin. J Clin Oncol 1999; 17: 1141–1145.

Armstrong

. Topotecan dosing guidelines in ovarian cancer: reduction and management of hematologic toxicity. Oncologist 2014; 9: 33–42.

Hesterberg

Banerji

Oren

et al.

Risk stratification for desensitization of patients with carboplatin hypersensitivity: clinical presentation and management. J Allergy Clin Immunol 2009; 123: 1262–1267.

Zorzou

Efstathiou

Galani

et al.

Carboplatin hypersensitivity reactions: a single institution experience. J Chemotherapy 2005; 17: 104–110.

Kandel

Loehr

Harter

et al.

Cisplatinum rechallenge in relapsed ovarian cancer patients with platinum reinduction therapy and carboplatin hypersensitivity. Int J Gynecol Cancer 2005; 15: 780–784.

Polyzos

Tsavaris

Kosmos

et al.

Hypersensitivity reactions to carboplatin administration are common but not always severe: a 10-year experience. Oncology 2001; 61: 129–133.

Castells

Tennant

Sloane

et al.

Hypersensitivity reactions to chemotherapy: outcomes and safety of rapid desensitization in 413 cases. J Allergy Clin Immunol 2008; 122: 574–580.

10.

Confino-Cohen

Fishman

Altaras

et al.

Successful carboplatin desensitization in patients with proven carboplatin allergy. Cancer 2005; 104: 640–643.

11.

Lee

Matulonis

Castells

. Rapid inpatient/outpatient desensitization for chemotherapy hypersensitivity: standard protocol effective in 57 patients for 255 courses. Gynecol Oncol 2005; 99: 393–399.

12.

Markman

Hsieh

Zanotti

et al.

Initial experience with a novel desensitization strategy for carboplatin-associated hypersensitivity reactions: carboplatin-hypersensitivity reaction. J Cancer Res Clin Oncol 2004; 130: 25–28.

13.

Rose

Fusco

Smrekar

et al.

Successful administration of carboplatin in patients with clinically documented carboplatin hypersensitivity. Gynecol Oncol 2003; 89: 429–433.

14.

Taylor

Beck

Krivak

et al.

Oxaliplatin salvage for recurrent ovarian cancer: a single institution's experience in patient populations with platinum resistant disease or a history of platinum hypersensitivity. Gynecol Oncol 2014; 134: 68–72.

15.

Robinson

Singh

Bodurka-Bevers

et al.

Hypersensitivity reactions and the utility of oral and intravenous desensitization in patients with gynecologic malignancies. Gynecol Oncol 2001; 82: 550–558.

16.

Lee

Matulonis

Castells

. Carboplatin hypersensitivity: a 6-h 12-step protocol effective in 35 desensitizations in patients with gynecological malignancies and mast cell/IgE-mediated reactions. Gynecol Oncol 2004; 95: 370–376.

17.

Goldberg

Confino-Cohen

Fishman

et al.

A modified, prolonged desensitization protocol in carboplatin allergy. J Allergy Clin Immunol 1996; 98: 841–843.

18.

Abe

Ikawa

. Desensitization treatment with cisplatin after carboplatin hypersensitivity reaction in gynecologic cancer. J Med Invest 2010; 57: 163–167.

19.

Tonkin

Rubin

Levin

. Carboplatin hypersensitivity: case reports and review of the literature. Eur J Cancer 1993; 29A: 1356–1357.

20.

Makrilia

Syrigou

Kaklamanos

et al.

Hypersensitivity reactions associated with platinum antineoplastic agents: a systematic review. Met Based Drugs 2010; 2010: 207084. .

21.

Sharma

Hamelin

. Classic histamine H1 receptor antagonists: a critical review of their metabolic and pharmacokinetic fate from a bird's eye view. Curr Drug Metab 2003; 4: 105–129.

22.

Pandey

Bhosale

Pandita

. Carboplatin hypersensitivity in relapsed ovarian carcinoma: a therapeutic challenge. Indian J Med Paediatr Oncol 2014; 35: 17–20.

23.

Gomez

Harter

Lück

et al.

Carboplatin hypersensitivity does introduction of skin test and desensitization reliably predict and avoid the problem? A prospective single-center study. Int J Gynecol Cancer 2009; 19: 1284–1287.

24.

Yip

Alfirevic

Pirmohamed

. Genetics of immune-mediated adverse drug reactions: a comprehensive and clinical review. Clin Rev Allergy Immunol 2015; 48: 165–175. .

25.

Sukasem

Puangpetch

Medhasi

et al.

Pharmacogenomics of drug-induced hypersensitivity reactions: challenges, opportunities and clinical implementation. Pac J Allergy Immuol 2014; 32: 111–123.

26.

Prmohamed

. Pharmacogenetics of idiosyncratic adverse drug reactions. Handb Exp Pharmacol 2010; 196: 477–491.

27.

Koshiba

Hosokawa

Kubo

et al.

Incidence of Carboplatin-related hypersensitivity reactions in Japanese patients with gynecologic malignancies. Int J Gynecol Cancer 2009; 19: 460–465.

28.

Sugimoto

Iwamoto

Murashima

et al.

Risk factors contributing to the development of carboplatin-related delayed hypersensitivity reactions in Japanese patients with gynecologic cancers. Cancer Chemother Pharmacol 2011; 67: 415–419.

29.

Hoekstra

Hurteau

Kirschner

et al.

The combination of monthly carboplatin and weekly paclitaxel is highly active for the treatment of recurrent ovarian cancer. Gynecol Oncol 2009; 115: 377–381.

30.

Gadducci

Tana

Teti

et al.

Analysis of the pattern of hypersensitivity reactions in patients receiving carboplatin retreatment or recurrent ovarian cancer. Int J Gynecol Cancer 2008; 18: 615–620.

31.

Schwartz

Bandera

Bradley

et al.

Does the platinum-free interval predict the incidence or severity of hypersensitivity reactions to carboplatin? The experience from women and infants' hospital. Gynecol Oncol 2007; 105: 81–83.

32.

Markman

Zanotti

Kulp

et al.

Relationship between a history of systemic allergic reactions and risk of subsequent carboplatin hypersensitivity. Gynecol Oncol 2003; 89: 514–516.

33.

Moon

Lee

Noonan

et al.

Deleterious BRCA1/2 mutations is an independent risk factor for carboplatin hypersensitivity reactions. Br J Cancer 2013; 109: 1072–1078.

34.

Mach

Lapp

Weddle

et al.

Adjunct histamine blockers as premedications to prevent carboplatin hypersensitivity reactions. Pharmacotherapy 2016; 36: 482–487.

35.

O'Cearbhaill

Zhou

Iasonos

et al.

The prophylactic conversion to an extended infusion schedule and use of premedication to prevent hypersensitivity reactions in ovarian cancer patients during carboplatin retreatment. Gynecol Oncol 2010; 116: 326–331.

36.

Pasternak

Link

Richardson

et al.

Effect of prophylactic extended-infusion carboplatin on incidence of hypersensitivity reactions in patients with ovarian, fallopian tube, or peritoneal carcinomas. Pharmacotherapy 2016; 36: 723–730.

37.

Joly

Ray-Coquard

Fabbro

et al.

Decreased hypersensitivity reactions with carboplatin-pegylated liposomal doxorubicin compared to carboplatin-paclitaxel combination: analysis from the GCIG CALYPSO relapsing ovarian cancer trial. Gynecol Oncol 2011; 122: 226–232.