PURPOSE OF REVIEW: Temsirolimus (Torisel) is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL). The recommended dosage in this indication (175 mg once weekly for 3 weeks and then 75 mg once weekly as maintenance) is higher than that for renal cell carcinoma; thus, the safety profile is quite different in the two indications. The aim of this review is to examine safety data for temsirolimus in MCL and provide guidance on the incidence and management of adverse events. Medline and EMBASE searches using the search terms 'temsirolimus' and 'mantle cell lymphoma'. FINDINGS: Four main published phase II-III clinical studies of temsirolimus in MCL were identified. Many adverse events are class-effect toxicities of mTOR inhibitors but, for others, often an accurate relationship with temsirolimus is difficult to assess with certainty. Haematological adverse events are the most frequently reported, but these are generally successfully managed by dose reductions or treatment delay. Gastrointestinal toxicity, especially diarrhoea, is a frequent and common adverse effect, but the incidence of grade 3-4 events is low. Other non-haematological toxicities include stomatological/dermatological and endocrinological adverse events. Incidence of these adverse events can be reduced by careful management and/or prevention. Grade 3 or higher pneumonitis, a known mTOR inhibitor-associated toxicity, was rarely reported in this indication, but the incidence was higher when temsirolimus was administered in combination with rituximab. Other adverse events include fatigue/asthenia, infection, hypersensitivity and extravasation. Sexual disorders, foetal malformations and psychiatric disorders are rarely reported. SUMMARY: Most temsirolimus-associated adverse events in patients with relapsed/refractory MCL are manageable, often without impacting administration of temsirolimus.
PURPOSE OF REVIEW: Temsirolimus (Torisel) is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL). The recommended dosage in this indication (175 mg once weekly for 3 weeks and then 75 mg once weekly as maintenance) is higher than that for renal cell carcinoma; thus, the safety profile is quite different in the two indications. The aim of this review is to examine safety data for temsirolimus in MCL and provide guidance on the incidence and management of adverse events. Medline and EMBASE searches using the search terms 'temsirolimus' and 'mantle cell lymphoma'. FINDINGS: Four main published phase II-III clinical studies of temsirolimus in MCL were identified. Many adverse events are class-effect toxicities of mTOR inhibitors but, for others, often an accurate relationship with temsirolimus is difficult to assess with certainty. Haematological adverse events are the most frequently reported, but these are generally successfully managed by dose reductions or treatment delay. Gastrointestinal toxicity, especially diarrhoea, is a frequent and common adverse effect, but the incidence of grade 3-4 events is low. Other non-haematological toxicities include stomatological/dermatological and endocrinological adverse events. Incidence of these adverse events can be reduced by careful management and/or prevention. Grade 3 or higher pneumonitis, a known mTOR inhibitor-associated toxicity, was rarely reported in this indication, but the incidence was higher when temsirolimus was administered in combination with rituximab. Other adverse events include fatigue/asthenia, infection, hypersensitivity and extravasation. Sexual disorders, foetal malformations and psychiatric disorders are rarely reported. SUMMARY: Most temsirolimus-associated adverse events in patients with relapsed/refractory MCL are manageable, often without impacting administration of temsirolimus.
Authors: Ajay K Gopal; Stefano R Tarantolo; Naresh Bellam; Damian J Green; Melissa Griffin; Tatyana Feldman; Anthony R Mato; Amy J Eisenfeld; Scott C Stromatt; Andre Goy Journal: Invest New Drugs Date: 2014-06-15 Impact factor: 3.850
Authors: Mizuki Nishino; Lauren K Brais; Nichole V Brooks; Hiroto Hatabu; Matthew H Kulke; Nikhil H Ramaiya Journal: Eur J Cancer Date: 2016-01-04 Impact factor: 9.162
Authors: Annelieke E C A B Willemsen; Jolien Tol; Nielka P van Erp; Marianne A Jonker; Maaike de Boer; Bob Meek; Paul C de Jong; Coline van Moorsel; Winald R Gerritsen; Jan C Grutters; Carla M L van Herpen Journal: Target Oncol Date: 2019-08 Impact factor: 4.493