Systemic Anti Cancer Treatment Protocol TEMSIROLIMUS in renal cell cancer PROTOCOL REF: MPHARTEMS (Version No: 1.0) Approved for use in: First-line treatment of adult patients with advanced renal cell carcinoma, who have at least three of six prognostic risk factors. Dosage: Drug Dosage Route Frequency Temsirolimus 25mg IV infusion Every 7 days, until disease progression or unacceptable toxicity Supportive treatments: Domperidone 10mg oral tablets, up to three times a day as required Extravasation risk: Temsirolimus: limited information, not thought to be vesicant. Symptomatic treatment and consider cold compress. Administration: Day Drug Dose Route Diluent and rate 1 Sodium Chloride 0.9% 50ml IV Infusion Flush 1 Chlorpheniramine 10mg IV Infusion 1 Temsirolimus 25mg IV Infusion 1 Sodium Chloride 0.9% 100ml IV Infusion Flush 30 minutes prior to temsirolimus In sodium chloride 0.9% over 30 60 mins Issue Date: 10 th June 2016 Page 1 of 5 Protocol reference: MPHARTEMS
Repeated every 7 days Hypersensitivity reactions: Patients should be observed closely for hypersensitivity reactions as reactions can occur very early in the first infusion, but may also occur with subsequent infusions. Mild-Moderate reaction: flushing or localised cutaneous reactions do not require interruption of therapy. Future doses must be pre-medicated with of IV chlorphenamine 10mg and IV hydrocortisone 100mg. Severe reactions: severe hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of temsirolimus and appropriate therapy. Drug Interactions Temsirolimus is metabolized by the cytochrome CYP3A4 pathway and therefore drugs that induce or inhibit this enzyme should be avoided where possible. INDUCERS (lowers temsirolimus levels): Carbamazepine, phenobarbital, phenytoin, dexamethasone, rifabutin, rifampicin, St John s Wort, troglitazone, pioglitazone INHIBITORS (increases temsirolimus levels): Indinavir, nelfinavir, ritonavir, clarithromycin, erythromycin, itraconazole, ketoconazole, nefazodone, grapefruit juice, verapamil, diltiazem, cimetidine, amiodarone, fluvoxamine, mibefradil ACE inhibitors concomitant use increases risk for angioedema. Main Toxicities: Skin rash, fatigue, mucostis, nausea, fluid retention, loss of appetite, increased blood glucose levels, neutropenia, and infection. Issue Date: 10 th June 2016 Page 2 of 5 Protocol reference: MPHARTEMS
Investigations and Treatment Plan: Medical Assessment Nursing Assessment Pre C1 D1 C2 D1 C3 D1 C4 D1 C5 D1 Ongoing X X X Every 4 weeks X X X X X Every cycle FBC X X X X X Every cycle U&E & LFT X X X X X Every cycle Fasting lipids and cholesterol X Every 12 weeks CT scan X Every 12 weeks Chest x-ray X X Informed Consent X PS recorded X X X X X X Toxicities documented X X X X X X If CT did not include chest Weight recorded X X X X X X Every cycle Random glucose X X X X Every 2 weeks Dose Modifications and Toxicity Management: Haematological toxicity Proceed on day 1 if:- WCC 3.0 x 10 9 /L Platelets 50 x 10 9 /L ANC 1.0 x 10 9 /L Delay 1 week on day 1 if:- WCC 2.9 x 10 9 /L Platelets <50 x 10 9 /L ANC 0.9 x 10 9 /L If WCC, Platelets or ANC still below required levels for treatment at week 2, delay treatment again and patient will need assessed and chemotherapy dose reduction by Oncologist Issue Date: 10 th June 2016 Page 3 of 5 Protocol reference: MPHARTEMS
Non-haematological toxicities Temsirolimus Stomatitis For Grade 2 toxicity: Temporary dose interruption until recovery to Grade 1. Re-initiate temsirolimus at same dose. If stomatitis recurs at Grade 2 or first occurrence at Grade 3, interrupt dose until recovery to Grade 1. Re-initiate temsirolimus at 20mg. Grade 4 toxicity: discontinue Metabolic events (hyperglycaemia, dyslipidaemia) Hyperglycaemia, dyslipidaemia (including hypercholesterolaemia and hypertriglyceridaemia) occur. Monitoring of blood glucose, blood cholesterol and triglycerides prior to the start of temsirolimus therapy and periodically thereafter, as well as management with appropriate medical therapy, is recommended. Grade 1 and 2 no dose adjustment required. Grade 3: Temporary dose interruption. Re-initiate temsirolimus at 20mg. Non-infectious pneumonitis Grade 2: Consider interruption of therapy until symptoms improve to Grade 1. And commence systemic corticosteroids. Re-initiate temsirolimus at 20mg. Discontinue treatment if failure to recover within 4 weeks. Grade 3: Interrupt temsirolimus until symptoms resolve to Grade 1. Consider re-initiating at 20mg, but if toxicity recurs at G3 then discontinue Consider opportunistic infections such as PCP in differential diagnosis. Empiric treatment: steroids and/or antibiotics. Other nonhaematological toxicities Grade 1 and Grade 2 tolerable: no dose adjustment required. Grade 2 intolerable: Temporary dose interruption until recovery to Grade 1. Re-initiate temsirolimus at same dose. If toxicity recurs then dose reduce to 20mg. Grade 3: As above, with re-initiation at 20mg. Issue Date: 10 th June 2016 Page 4 of 5 Protocol reference: MPHARTEMS
References: http://www.medicines.org.uk/emc/medicine/21260 Issue Date: 10 th June 2016 Page 5 of 5 Protocol reference: MPHARTEMS