Reactions 1184 - 12 Jan 2008

★ SCetuximab

Fatal diffuse alveolar damage (first report) in lungtransplant recipients: 2 case reports

Two male left lung transplant recipients developed diffusealveolar damage (DAD) after receiving cetuximab formetastatic cutaneous squamous cell cancer (cSCC), andsubsequently died.

A 59-year-old man developed cSCC 6 years after undergoingtransplantation. Despite repeated resections and radiotherapy,cSCC recurred and metastasised, and he subsequentlyreceived three cetuximab injections over 4 weeks [exactdosage not stated] after undergoing left posterolateral neckdissection and near total scalp excision. One week after thethird injection, he developed worsening dyspnoea with anoxygen saturation of 60%, and a high-resolution CT scanshowed ground-glass opacities throughout his transplantedleft lung. As he was receiving reduced-intensityimmunosuppression (prednisone, mycophenolate mofetil andsirolimus), on admission, acute rejection was stronglysuspected and IV methylprednisolone was initiated.Examination identified crackles in his transplanted lung anddiminished breath sounds in his right lung. Despite empiricaltreatment with pentamidine, ganciclovir, voriconazole,vancomycin and piperacillin/tazobactam, he showed noimprovement and developed atrial fibrillation, progressiverenal failure, acidosis and transaminitis. He died 10 days afterhospitalisation. Autopsy identified bilateral DAD with alveolarseptal thickening and prominent hyaline membranes.

A 67-year-old man, who had undergone transplantation3 years earlier, developed cSCC and underwent resection;cSCC subsequently recurred and metastasised. Hisimmunosuppressive regimen was reduced, and he receivedpaclitaxel and carboplatin, which were discontinued due todeep vein thrombosis and pulmonary embolism. He thenreceived cetuximab [dosage not stated] and radiotherapy. Oneweek after receiving cetuximab, he developed progressivedyspnoea and a non-productive cough, and had an oxygensaturation of 52%. On examination, he had diminished breathsounds in his right lung and crackles in his transplanted lung. Achest CT scan showed bullous emphysema and a chronicpneumothorax on his right lung, and ground-glass opacitiesthroughout his transplanted lung. As he was receiving reducedimmunosuppression (prednisone and sirolimus), acuterejection was considered the most likely diagnosis, and hereceived IV methylprednisolone, in addition to empiricalantibacterial, antifungal and anti-cytomegalovirus therapies.He failed to improve, and died, 22 days post-admission, withrespiratory failure. An autopsy showed focal organisingpneumonia, and organising DAD with hyaline membraneformation.

Author comment: "[W]e speculate that [epidermal growthfactor receptor] may play an essential role in the transplantedlung and that [epidermal growth factor receptor] blockadewith cetuximab may be associated with rapid-onset DAD."Leard LE, et al. Fatal diffuse alveolar damage in two lung transplant patientstreated with cetuximab. Journal of Heart and Lung Transplantation 26: 1340-1344,No. 12, Dec 2007 - USA 801079492

» Editorial comment: A search of AdisBase and Medline didnot reveal any previous case reports of diffuse alveolar damageassociated with cetuximab. The WHO Adverse Drug Reactionsdatabase contained three reports of adult respiratory distresssyndrome associated with cetuximab.

1

Reactions 12 Jan 2008 No. 11840114-9954/10/1184-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved