CASE REPORT

Cystoid macular edema induced by nab-paclitaxel

Yuko Tanaka • Hiroko Bando • Hisato Hara •

Yasuaki Ito • Yoshifumi Okamoto

Received: 6 February 2012 / Accepted: 18 April 2012

� The Japanese Breast Cancer Society 2012

Abstract Cystoid macular edema (CME) is a rare com-

plication of taxane-based chemotherapy. We encountered a

patient who developed CME during treatment with nab-

paclitaxel for metastatic breast cancer. Early detection of

this disease enables continuation of appropriate treatment

without reducing the quality of life for patients with end-

stage disease. Physicians should be aware of this potential

adverse effect, and should make changes to the treatment

of patients as soon as possible.

Keywords Nab-paclitaxel � Breast cancer � Cystoid

macular edema

Abbreviations

CME Cystoid macular edema

OCT Ocular coherence tomography

Introduction

Nab-paclitaxel is an anticancer agent (protein-bound pac-

litaxel) approved for treatment of breast cancer. It remedies

problems related to the hydrophobicity of paclitaxel and

does not require the use of solvents, for example poly-

oxyethylated castor oil or ethanol, which are associated

with toxic responses, for example hypersensitivity

reactions and prolonged sensory neuropathy. Moreover,

nanoparticle technology enables selective delivery of large

amounts of this anticancer drug to the tumor.

Cystoid macular edema (CME) is a rare adverse event

associated with nab-paclitaxel, although some previous

reports suggest it associated with all of the taxane drugs,

for example docetaxel, paclitaxel, and nab-paclitaxel.

We report here a patient with CME associated with nab-

paclitaxel which resolved on discontinuation of the drug.

Case presentation

A 47-year old female with a diagnosis of breast cancer

metastatic to the bone, lung, pleura, and lymph nodes noticed

discomfort and decreasing vision, without pain, in the left

eye, lasting 1 month. The patient was a postmenopausal

woman because of previous long-term chemotherapy for

management of metastatic breast cancer. At that time, she

had been receiving protein-bound paclitaxel (nab-paclit-

axel), and had undergone seven courses at a dose of 400 mg

(260 mg per m2 body surface area) every 3 weeks as her

sixth-line anticancer treatment after she was diagnosed with

the recurrence of breast cancer. She had also been receiving

zoledronic acid at a dose of 4 mg every 4 weeks.

The patient’s family history was unremarkable with

regard to malignant disease. There were no complications,

for example hypertension nor diabetes. Her first admission

for the breast cancer was in 1998, and she had undergone

surgery. Histologically, the tumor was weakly positive for

estrogen receptor expression and negative for the proges-

terone receptor and erbB2.

The patient received adjuvant chemotherapy with cyclo-

phosphamide, methotrexate, and fluorouracil combination

chemotherapy sequentially with tamoxifen for 5 years. In

Y. Tanaka (&) � H. Bando � H. Hara

Department of Breast, Thyroid and Endocrine Surgery, Tsukuba

University, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan

e-mail: choshi_sai_yuu@k6.dion.ne.jp;

yutanakayu@md.tsukuba.ac.jp

Y. Ito � Y. Okamoto

Department of Ophthalmology, Tsukuba University,

1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan

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Breast Cancer

DOI 10.1007/s12282-012-0373-y

2005, she developed lung and pleural metastases. She was

treated with multiple lines of chemotherapy, for example

doxorubicin and docetaxel, then subsequently docetaxel

monotherapy. In 2006, she developed bone metastases and

received capecitabine and a bisphosphonate (pamidronate

followed by zoledronate) and, subsequently, vinorelbine,

S-1, and letrozole. In 2010, she progressed systemically and

was switched nab-paclitaxel at the above-mentioned dose.

Although her systemic condition was stable and she had

tolerable slight sensory discomfort (Grade 1), 4 months after

the initial administration of nab-paclitaxel (the agent had

been administered seven times), she complained of a

decrease in vision in her left eye with an anorthopia. She had

no increase in tear production. The patient’s visual acuity

was 20/16 OD and 20/40 OS. The pupils, extraocular

motility, and confrontation visual fields were within normal

limits. Funduscopy revealed a slight decrease in the trans-

parency of the left macula area (Fig. 1a). Fluorescein fundus

angiography revealed a left cystic macular edema (CME)

with floriform leakage from the parafoveal capillaries

(Fig. 1b). Ocular coherence tomography (OCT) revealed

cystic space in the retina, thereby confirming CME (Fig. 1c).

The nab-paclitaxel treatment was discontinued, and she

was treated conservatively without use of ophthalmic

medication, for example topical steroids or anti-inflam-

matory drugs. She experienced gradual recovery of her

visual function, and her visual acuity had improved

2 months later.

Discussion

Nab-paclitaxel is a new anticancer agent approved for

treatment of breast cancer. Paclitaxel, a member of the

taxane family of microtubule-stabilizing agents and the

first licensed formation of paclitaxel (CrEL-paclitaxel), has

been used for a long time. However, its hydrophobic nature

results in poor solubility. The CrEL formulation can cause

hypersensitivity reactions, and to avoid this adverse effect

additional use of steroids and antihistamines is necessary.

In addition, special infusion tubing and inline filters are

needed when administering CrEL-paclitaxel.

Nab-paclitaxel improves the pharmacokinetic properties

of paclitaxel and facilitates administration of the agent.

Another advantage of this new agent is delivery of more

drug to the tumor compared with CrEL-paclitaxel, which is

thought to increase its antitumor effects. In fact, clinical

trials have shown that the efficacy of nab-paclitaxel is

Fig. 1 a Fundoscopic appearance of both eyes showing a slight decrease of transparency in the left macula area. b Fluorescein fundus

angiography revealing a left CME with floriform leakage from the parafoveal capillaries. c OCT revealed cystic space in the retina in the left eye

Breast Cancer

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significantly better than that of CrEL-paclitaxel. The safety

profile was almost the same for both agents, although

sensory neuropathy was significantly more common in the

nab-paclitaxel group [1].

With regard to taxanes, ophthalmic adverse effects

including reduced vision, scintillating scotomas, and

abnormal visual evoked potentials can occur, although

these are relatively uncommon. Some reports have also

indicated that CME can occur as a result of administration

of taxanes [2–5]. CME as a result of taxanes usually occurs

in both eyes (Table 1). Although it is unclear why CME

occurred unilaterally in this case, it may be because we

detected the CME at an early stage, before it became

bilateral.

Macular edema is a condition characterized by abnormal

thickening of the retina associated with the accumulation of

excess fluid in the extracellular space of the neurosensory

retina. The typical fluorescein angiographic appearance of

CME is small focal leaks early in the disease which

increase in size and intensity resulting in late pooling in a

characteristic flower petal pattern with or without leakage

surrounding the optic nerve [4]. Although CME can occur

in association with a variety pathological conditions, it

most often develops in association with inflammation or

after cataract extraction. CME may occur in a diffuse

pattern or with a characteristic petalloid appearance, and

this pattern of CME has previously been observed in a

patient receiving CrEL-paclitaxel. Cessation of treatment

of the patient with this agent led to improvement of visual

acuity and resolution of the macular edema [5]. Although

basic treatment of CME is alleviation of the edema, dis-

continuation of the taxane sometimes leads to improvement

of visual acuity and fundoscopic findings without addi-

tional treatment for CME. Steroidal or non-steroidal

inflammatory drugs or acetazolamide have previously been

used for treatment of CME [2–7] (Table 1).

Taxanes induce fluid retention, and although this may

result in CME, the pathogenesis of drug-induced CME is

still unclear. Even if the CME is reversible, early diagnosis

and treatment are needed, so physicians should be aware

that CME is a rare complication of treatment with taxanes,

including nab-paclitaxel.

Conclusion

We report herein a case of CME that developed during use

of nab-paclitaxel for treatment of a patient with metastatic

breast cancer. Physicians should be aware that CME is a

potential adverse event related to taxane treatment, but that

the condition is reversible if the agent is discontinued.

References

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Table 1 The characteristics of

CME patients described in

previous reports

a Taxanes were discontinued

for all patients

Case Age Affected side Treatmenta Time to recovery Offending drug

1 40 Bilateral Observation only 4 months nab-paclitaxel

2 56 Bilateral Observation only 4 weeks nab-paclitaxel

3 65 Bilateral Steroids and non-steroidal

anti-inflammatory drugs

2 weeks nab-paclitaxel

4 58 Bilateral Observation only 3 months nab-paclitaxel

5 60 Bilateral Acetazolamide 6 months Docetaxel

6 53 Bilateral Observation only 8 months Docetaxel

7 63 Bilateral Observation only 6 weeks CrEL-paclitaxel

8 62 Bilateral Acetazolamide 6 weeks CrEL-paclitaxel

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