Granulocytopenia

INTRODUCTION: Vinorelbine (Navalbine), a newer Vinca alkaloid has been increasingly used in the chemotherapy of non-small-cell Bronchogenic carcinoma & metastatic breast carcinoma. Initially, it appeared to have a favorable side-effect profile with dose & duration limited myelo-suppression (Granulocytopenia, Thrombocytopenia) being the major toxicityl. With more frequent use of Vinorelbine, new side effects of this drug are being reported. We are reporting a case of Interstitial Pneumonitis developing after Vinorelbine therapy for Bronchoalveolar carcinoma.

CASE PRESENTATION: K.K. 46 year old farmer smoker presented to our OPD with complaints of dull diffuse chest pain on right side, cough with mucoid expectoration >200 ml/d & breathlessness. On physical examination breath sounds were diminished in intensity on right side, coarse crept was present in mid & lower chest. Chest X-Ray revealed diffuse heterogenous infiltrates with air-bronchogram in right lung. Patient was previously treated for bronchopneumonia with broad-spectrum antibiotics elsewhere but had no improvement. Considering the possibility of malignancy, Fibre-Optic Bronchoscopy revealed excessive mucoid secretions. Bronchial-brush and Bronchoscopic-lavage was negative for microbiology & cytology, so lung biopsy was done, it showed bronchoalveolar carcinoma. CT-scan chest revealed, focal area of apparent parenchymal consolidation with linear strands extending to the periphery. After complete evaluation & basic investigation {Complete Blood Count (CBC), Liver Function Test, Renal Function Test} we planned chemotherapy with Vinorelbine, hence Vinorelbine 50 mg (as the body surface area was 1.68m2) over 10 minutes was infused after proper hydration, patient tolerated the drug well & after observation for 1 day, he was discharged on request. After 3 days, patient returned with complaints of increasing dyspnoea, dry cough & severe distress. He was tachycardiac, accessory muscles of respiration was working, breath sounds were diminished and of bronchial nature on right side, Chest X-Ray revealed extensive consolidation on whole of right lung. His CBC was normal & sputum for Gram stain/culture was negative. However because of suspicion of community-acquired-pneumonia, broad-spectrum antibiotic & intravenous steroids were started, patient responded well with clearance of radiological-infiltrates. Next week, IInd cycle of Vinorelhine 50 mg over 10 minutes was given & on IInd day of IInd cycle patients again developed breathlessness & dry cough. CXR showed homogenous consolidation with air-bronchogram in right lung. This time considering the possibility of Vinorelbine induced pneumonitis, Trans-bronchial-lung-Biopsy was done revealing focal fibrosis, eosinophilic-proteinaceous exudate & reactive proliferation of type-II-pneumocytes, diffuse alveolar damage & hyaline-membrane. Patient was put only on intravenous methyl-prednisolone 5O0-mg 8-hourly & symptomatic treatment. After 3days of treatment he responded with some clearance of radiographic infiltrates, hence confirming the diagnosis of Vinorelbine induced Interstitial Pneumonitis.

DISCUSSIONS: This is probably the first case-report documenting Interstitial Pneumonitis after Vinorelbine administration. The clinical course, radiological & pathologic characteristics, rapid response to steroid & absence of other potential causes are suggestive of drug-induced pneumonitis. Many chemo-therapetic agents like bleomycin, busulfan have been implicated with development of interstitial pneumonitis, but this is probably the first case-report of Vinorelbine induced interstitial pneumonitis The mechanism is unknown, but is believed to be an allergic-immunological process as is shown by rapid & near-complete response after drug cessation & steroids.

CONCLUSION: Vinorelbine toxicity should be strongly considered in diagnosis of interstitial pneumonitis developing after short period of administration, urgent diagnostic workup is essential to exclude other etiology & to establish drug as a cause of interstitial pneumonitis & to enable early institution of steroid therapy which given prompt response.

REFERENCES:

(1) Roland T. Skeel. Anti-Neoplastic drugs & biologic response modifiers: classification use & toxicity of clinically useful agents. In Handbook of Cancer Chemotherapy. Ed. Roland T. Skeel. V ed. P.142, 1999. Lippincott, Williams & Wilkins.

DISCLOSURE: Mayank Vats, None.

Mayank Vats MD * Rakesh C. Gupta MD Deepa V. Khandelwal MBBS Neeraj Gupta MD Pramod Dadhich MD J.L.N. Medical College, Ajmer, Rajasthan, India

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