Docetaxel-induced myositis: report of a novel side-effect. Clinical-scientific Notes

Internal Medicine Journal 2005; 35: 369–370

LETTERS TO THE EDITOR CLINICAL–SCIENTIFIC NOTES Docetaxel-induced myositis: report of a novel side-effect A 47-year-old premenopausal woman presented in November 2002 with a right axillary mass. Examination revealed enlarged right axillary nodes, but no breast masses or other lymphadenopathy. Biopsy showed metastatic oestrogen and progesterone receptor (ER and PR) positive carcinoma. Bilateral mammography, ultrasonography, bone scan and computerized tomography showed no evidence of cancer elsewhere. Magnetic resonance imaging (MRI) of both breasts revealed an asymmetric density with delayed enhancement in the upper outer quadrant of the right breast. A biopsy of this region was non-diagnostic. Axillary nodal dissection was carried out on 20 November 2002. Histopathology revealed a carcinoma involving 29 of 37 nodes with extranodal spread. ER and PR staining was strongly positive, but negative for HER-2/neu. She was also known to have hypertension on ramipril, and type II diabetes mellitus requiring insulin. The patient was managed as an occult right primary breast cancer with extensive axillary nodal involvement and offered adjuvant chemotherapy with a programme of four cycles of EC (epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2) every 3 weeks, with dexamethasone and ondansetron premedication, followed by four cycles of docetaxel (100 mg/m2) every 3 weeks with dexamethasone and metoclopramide premedication. Chemotherapy was to be followed by radiotherapy to the right breast, supraclavicular fossa and axilla and 5 years of adjuvant tamoxifen. EC chemotherapy commenced on 19 December 2002 and was generally well tolerated. Cycle one of docetaxel (total dose 180 mg) was commenced on 20 March 2003 and was complicated by grade two stomatitis and diarrhoea. The patient also complained of bilateral foot pain occurring on days 4–9 post docetaxel. This resolved prior to cycle two and examination at that time was unremarkable aside from stomatitis. Therefore, cycle two was delayed by 1 week and subsequent doses reduced by 20% (total dose 145 mg each cycle). Following cycle two the patient again developed bilateral foot pain that resolved prior to cycle three. On 30 May 2003, 3 weeks post docetaxel, the patient presented with a 10-day history of bilateral severe pain and weakness in the proximal leg muscles associated with difficulty transferring and walking. Physical examination revealed a waddling gait with extremely tender quadriceps muscles. Both thighs were warm to the touch and swollen with proximal muscle weakness (power 4/5).

The examination was otherwise unremarkable, including no rash. Investigations revealed a neutrophilia of 14.1 × 109/L, a raised erythrocyte sedimentation rate of 77 mm/h (range 1–30 mm/h) and a raised C-reactive protein (CRP) of 34 mg/L (range 0–10 mg/L). Blood counts and a standard biochemical screen were otherwise unremarkable. Serum creatine phosphokinase (CPK) was markedly elevated at 4558 U/L (range 20–200 U/L). Other laboratory results included a low antinuclear antibody speckled titre of 1:80 with negative antidouble stranded DNA antibodies and extractable nuclear antibodies. The serum vitamin D level was low at 16 nmol/L (range 70–100 nmol/L). A provisional diagnosis of docetaxel-induced myositis was made. Management included opioid analgesia, dexamethasone (initially 4 mg/day for 2 days, reduced to 2 mg/day for 2 days, then 1 mg for 2 days) and vitamin D supplementation. Serum CPK levels fell rapidly (Table 1) and the patient was sufficiently mobile to be discharged home 6 days after admission. The fourth cycle of docetaxel was abandoned and radiotherapy commenced shortly thereafter. There was no residual muscle pain or proximal myopathy on completion of radiotherapy or at subsequent follow up. Docetaxel is a cytotoxic taxane synthesized by the addition of a side-chain to an inactive precursor found in the needles of yew trees.1 Like paclitaxel, docetaxel promotes the assembly of tubulin polymer subunits into stable microtubules and inhibits their disassembly.2 The stabilized microtubules inhibit the proliferation of cells, which then undergo apoptosis.3 In Australia, docetaxel is approved for advanced breast cancer, metastatic ovarian cancer and locally advanced or metastatic non-small cell lung cancer and shows encouraging activity in prostate cancer. The dose-limiting toxicity of docetaxel is myelosuppression.1 Although neuromuscular side-effects such as myalgia and neuropathy have been reported after docetaxel,1,4 these side-effects are more common after paclitaxel, which has been reported to cause myositis,4 Table 1 Serial creatine phosphokinase (CPK) levels Date 30/5/03 31/5/03 1/6/03 2/6/03 3/6/03 4/6/03 Normal range 20–200 U/L.

CPK level (U/L) 4558 4386 2978 2254 1177 1002

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Letters to the Editor

possibly because of the accumulation of acid phosphatase in muscle lysosomes.5 A recent literature search has not revealed any previous reports of docetaxel-induced myositis. Although neither a muscle biopsy nor electromyography was carried out, the clinical features suggest a myositis secondary to docetaxel. The relevance of the concurrent vitamin D deficiency remains uncertain. Vitamin D deficiency may cause a proximal myopathy, but not myositis.6 Polymyositis and dermatomyositis are recognized as rare manifestations of malignancy, but are usually present at diagnosis or in the context of metastatic disease.7 The patient had no features suggestive of other causes of myositis, such as polymyositis or another connective tissue disorder. The other medications administered (including chemotherapeutic agents, antiemetics, ramipril and insulin) are unlikely to cause myositis. There are no reports of epirubicin or cyclophosphamide associated myositis. The bilateral foot pain post docetaxel probably represented an unrecognized hand–foot syndrome. In conclusion, this case outlines an episode of docetaxel-induced myositis, a previously unreported side-effect of docetaxel. Further experience with docetaxel is revealing less common side-effects, such as hand–foot syndrome and the myositis reported here. These rarer side-effects may become more important in future clinical practice as the use of docetaxel increases. Received 17 August 2004; accepted 6 October 2004.

HUGHES1

B. G. M. R. STUART-HARRIS2 1Thoracic/Medical Oncology Unit, The Prince Charles Hospital, Rode Rode, Chermside, Queensland

Internal Medicine Journal 2005; 35: 369–370

and Oncology Unit, The Canberra Hospital, Woden, Australian Capital Territory, Australia 2Medical

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