complete regression of choroidal metastases from breast cancer after docetaxel-based systemic...

2
BRIEF REPORT Complete Regression of Choroidal Metastases From Breast Cancer After Docetaxel-Based Systemic Chemotherapy Christos Kosmas, MD,* Nikolaos A. Malamos, MD, and Minas Antonopoulos, MD Key words: Choroidal metastasis; breast cancer; docetaxel; mitoxanthrone Metastatic breast cancer represents a disease setting where chemotherapy is at best a palliative measure with limited prospective for prolonged survival. Certain meta- static sites, such as the choroid, have been traditionally considered particularly difficult to treat. Radiation therapy (RT) has been administered successfully for symptom control and palliation, with an 80% responses rate. RT, moreover, prevents blindness [1]. Chemo- therapy has been anecdotally reported to be as effective as radiotherapy for choroidal metastases [2]. Newer che- motherapeutic agents, such as taxanes (paclitaxel and docetaxel) have proven efficacy in pre-treated or chemo- therapy naive patients with metastatic breast cancer [3]. Their combinations with anthracyclines or anthrace- diones (mitoxantrone) are currently considered the most active two-drug regimens in breast cancer. Our experi- ence with these drugs in a woman with breast cancer metastatic to the choroid, lung, skin and lymph nodes is of interest, since chemotherapy was applied as the sole treatment modality. The patient was a 43-year-old premenopausal woman with a node-positive and hormone receptor-positive in- filtrative ductal carcinoma. Three years after primary management with surgery and adjuvant chemotherapy (CMF), she presented with loss of visual acuity and float- ers on her right eye. Chest CT scan revealed multiple pulmonary nodules compatible with secondary meta- static deposits. Ophthalmoscopic examination and MRI scan of the brain disclosed an ocular mass involving the posterior pole of the right eye (Fig. 1A). She was treated with a combination chemotherapy regimen of docetaxel; 100 mg/m 2 i.v. on day 1 in 1-hr infusion (after premedi- cation with 20 mg dexamethasone, 50 mg ranitidine and 4 mg dimethidene maleate) and mitoxanthrone; 20 mg/ m 2 i.v. on day 8 in a 15 min infusion, recycled every 3 weeks for 6 cycles. Given the highly myelosuppressive potential of the regimen established in a prior phase I study, prophylactic granulocyte-colony stimulating fac- tor (glycosylated recombinant human G-CSF, lenogras- tim; granocytet) 33.6 iu/day was administered subcuta- neously on days 2-6 and 10-16 or until achieving a stable unsupported neutrophil count of 1500/ml. Treatment was well tolerated with minimal toxicity; grade 2 mucositis and uncomplicated grade 4 neutropenia of 3-days dura- tion. Her visual symptoms improved rapidly and regres- sion was seen on fundoscopy. After the end of the che- motherapy course the pulmonary metastases disappeared and the brain MRI demonstrated complete regression of the uveal deposit (Fig. 1B). Fluoroangiography of her eyes revealed a choroid scar compatible with regression and healing of the choroidal metastasis on the right eye. She was then put on hormonal therapy with megestrol acetate tablets 160 mg o.d. Eighteen months after the initiation of chemotherapy for metastatic disease the pa- tient was in complete remission with no recurrence of her visual symptoms, reappearrance of any pulmonary le- sion, or any new metastatic disease site. DISCUSSION Choroidal metastases represent the most common ma- lignant tumors of the adult eye. Shields et al. [4] report that uveal metastases arise from a primary cancer of the breast in 47%, lung in 21%, gastrointestinal tract in 4%, kidney in 2%, skin in 2%, prostate in 2% and other cancers in 4%, whereas in 17% no primary site could be identified [4]. Traditionally, choroidal metastases have been man- aged with othovoltage radiotherapy and stereotactic ra- diosurgery yielding an overall response rate of 70–80% in the eye, associated with improvement in visual acuity [2, 5, 6]. There are however only anecdotal reports of patients with breast cancer who responded completely to multi-drug chemotherapy regimens administered for widespread metastatic disease [2, 7]. Logani et al. re- Department of Medicine, Hematology & Medical Oncology Unit, Hel- ena-Venizelou Hospital, Athens, Greece. *Corresponding author: Christos Kosmas, M.D., Medical Oncologist, 21 Apolloniou Street, GR-16341 Athens, Greece. E-mail: [email protected] Medical and Pediatric Oncology 34:229–230 (2000) © 2000 Wiley-Liss, Inc.

Upload: minas

Post on 06-Jun-2016

212 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Complete regression of choroidal metastases from breast cancer after docetaxel-based systemic chemotherapy

BRIEF REPORTComplete Regression of Choroidal Metastases From Breast Cancer After

Docetaxel-Based Systemic Chemotherapy

Christos Kosmas, MD,* Nikolaos A. Malamos, MD, and Minas Antonopoulos, MD

Key words: Choroidal metastasis; breast cancer; docetaxel; mitoxanthrone

Metastatic breast cancer represents a disease settingwhere chemotherapy is at best a palliative measure withlimited prospective for prolonged survival. Certain meta-static sites, such as the choroid, have been traditionallyconsidered particularly difficult to treat. Radiationtherapy (RT) has been administered successfully forsymptom control and palliation, with an 80% responsesrate. RT, moreover, prevents blindness [1]. Chemo-therapy has been anecdotally reported to be as effectiveas radiotherapy for choroidal metastases [2]. Newer che-motherapeutic agents, such as taxanes (paclitaxel anddocetaxel) have proven efficacy in pre-treated or chemo-therapy naive patients with metastatic breast cancer [3].Their combinations with anthracyclines or anthrace-diones (mitoxantrone) are currently considered the mostactive two-drug regimens in breast cancer. Our experi-ence with these drugs in a woman with breast cancermetastatic to the choroid, lung, skin and lymph nodes isof interest, since chemotherapy was applied as the soletreatment modality.

The patient was a 43-year-old premenopausal womanwith a node-positive and hormone receptor-positive in-filtrative ductal carcinoma. Three years after primarymanagement with surgery and adjuvant chemotherapy(CMF), she presented with loss of visual acuity and float-ers on her right eye. Chest CT scan revealed multiplepulmonary nodules compatible with secondary meta-static deposits. Ophthalmoscopic examination and MRIscan of the brain disclosed an ocular mass involving theposterior pole of the right eye (Fig. 1A). She was treatedwith a combination chemotherapy regimen of docetaxel;100 mg/m2 i.v. on day 1 in 1-hr infusion (after premedi-cation with 20 mg dexamethasone, 50 mg ranitidine and4 mg dimethidene maleate) and mitoxanthrone; 20 mg/m2 i.v. on day 8 in a 15 min infusion, recycled every 3weeks for 6 cycles. Given the highly myelosuppressivepotential of the regimen established in a prior phase Istudy, prophylactic granulocyte-colony stimulating fac-tor (glycosylated recombinant human G-CSF, lenogras-tim; granocytet) 33.6 iu/day was administered subcuta-neously on days 2-6 and 10-16 or until achieving a stable

unsupported neutrophil count of 1500/ml. Treatment waswell tolerated with minimal toxicity; grade 2 mucositisand uncomplicated grade 4 neutropenia of 3-days dura-tion. Her visual symptoms improved rapidly and regres-sion was seen on fundoscopy. After the end of the che-motherapy course the pulmonary metastases disappearedand the brain MRI demonstrated complete regression ofthe uveal deposit (Fig. 1B). Fluoroangiography of hereyes revealed a choroid scar compatible with regressionand healing of the choroidal metastasis on the right eye.She was then put on hormonal therapy with megestrolacetate tablets 160 mg o.d. Eighteen months after theinitiation of chemotherapy for metastatic disease the pa-tient was in complete remission with no recurrence of hervisual symptoms, reappearrance of any pulmonary le-sion, or any new metastatic disease site.

DISCUSSION

Choroidal metastases represent the most common ma-lignant tumors of the adult eye. Shields et al. [4] reportthat uveal metastases arise from a primary cancer of thebreast in 47%, lung in 21%, gastrointestinal tract in 4%,kidney in 2%, skin in 2%, prostate in 2% and othercancers in 4%, whereas in 17% no primary site could beidentified [4].

Traditionally, choroidal metastases have been man-aged with othovoltage radiotherapy and stereotactic ra-diosurgery yielding an overall response rate of 70–80%in the eye, associated with improvement in visual acuity[2, 5, 6]. There are however only anecdotal reports ofpatients with breast cancer who responded completely tomulti-drug chemotherapy regimens administered forwidespread metastatic disease [2, 7]. Logani et al. re-

Department of Medicine, Hematology & Medical Oncology Unit, Hel-ena-Venizelou Hospital, Athens, Greece.

*Corresponding author: Christos Kosmas, M.D., Medical Oncologist,21 Apolloniou Street, GR-16341 Athens, Greece.E-mail: [email protected]

Medical and Pediatric Oncology 34:229–230 (2000)

© 2000 Wiley-Liss, Inc.

Page 2: Complete regression of choroidal metastases from breast cancer after docetaxel-based systemic chemotherapy

ported a patient with breast cancer, strongly positive forestrogen receptors, responded to anti-estrogen hormonetherapy [8]. Thus, in our patient, hormonal treatmentwith megestrol acetate might have contributed to themaintenance of the response achieved by chemotherapy.

In conclusion, our experience and that of others sug-gests that choroidal metastases, like visceral deposits,from breast carcinoma can respond to systemic chemo-therapy. Moreover, our patient is the first to our knowl-edge in whom a complete response was achieved using adocetaxel-based multiple drug combination.

ADDENDUM

Since the submission/acceptance of this report, thepatient under discussion developed leptomeningeal car-cinomatosis presenting with right facial nerve palsy ofperipheral type and headaches 21 months after the ini-tiation of docetaxel-based chemotherapy. Leptomeninge-al dissemination was confirmed by a new brain MRIrevealing meningeal deposits and cerebrospinal fluid (CSF)cytologic examination demonstrating clusters of malignantcells. She was treated by whole brain radiotherapy and in-tensive intrathecal methotrexate leading to complete remis-

sion. She remains without evidence of disease 6 monthssince the diagnosis of leptomeningeal carcinomatosis.

REFERENCES

1. Thatcher N, Thomas PR. Choroidal metastases from breast carci-noma: a survey of 42 patients and the use of radiation therapy.Clin Radiol 1975;26:549–553.

2. Letson AD, Davidorf FH, Bruce RA Jr. Chemotherapy for treat-ment of choroidal metastases from breast carcinoma. Am J Op-thalmol 1982;93:102–106.

3. Chevallier B, Fumoleau P, Kerbrat P, et al. Docetaxel is a majorcytotoxic drug for the treatment of advanced breast cancer: aphase II trial of the Clinical Screening Cooperative Group of theEuropean Organization for Research and Treatment of Cancer. JClin Oncol 1995;13:314–322.

4. Shields CL, Shields JA, Gross NE, et al. Survey of 520 eyes withuveal metastases. Ophthalmology 1997;104:1265–1276.

5. Maor M, Chan RC, Young SE. Radiotherapy of choroidal metas-tases: breast cancer as primary site. Cancer 1977;40:2081–2086.

6. Sassmannshausen J, Bornfeld N, Foerster MH, et al. Metastases ofmalignant extra-ocular tumors to the choroid. Diagnosis and frac-tionated radiotherapy. Fortschr Opthalmol 1990;87:69–73.

7. Brinkley JR Jr. Response of a choroidal metastasis to multiple-drug chemotherapy. Cancer 1980;45:1538–1539.

8. Logani S, Gomez H, Jampol LM. Resolution of choroidal metsta-sis in breast cancer with high estrogen receptors. Arch Opthalmol1992;110:451–452.

Fig. 1. (A) MRI scan of the brain revealing a flat ocular mass involving the posterior pole of the right eye.(B) After six cycles of chemotherapythe brain MRI demonstrates complete regression of the uveal deposit.

230 Kosmas et al.