Herceptin IV (Trastuzumab) and Paclitaxel Cumbria, Northumberland, Tyne & Wear Area Team

Transcription

1 DRUG ADMINISTRATION SCHEDULE Given as a three weekly schedule Day Drug Daily Dose Route Diluent & Rate On first cycle 250mls Normal Saline Herceptin IV 8 mg/kg Infusion only 90 mins On other 250mls Normal Saline Herceptin IV 6 mg/kg Infusion cycles 30 to 90 mins Day Drug Daily Dose Route Diluent & Rate Sodium Chloride 0.9% 100ml Infusion Fast Running Ondansetron 8mg Oral /Slow bolus/15 min infusion Chlorpheniramine 10 mg Iv bolus Via saline drip Ranitidine 50 mg Iv bolus Via saline drip Dexamethasone See below* Iv bolus Via saline drip Day 1,8,15 (Give on the day after trastuzumab on first dose) Paclitaxel 175 mg/m 2 Infusion 500mls 5% Dextrose or N/Saline 3 hours (start infusion very slowly) *Ondansetron IV must be infused over 15 minutes in patients over 65 years of age. NOTE ON DOSE FORMS 1. Herceptin subcutaneous (SC) may be substituted for Herceptin IV. Herceptin SC is given at a dose of 600mg over 5mins by subcutaneous injection into alternating thighs. See separate SC protocol for full administration details 2. There is also a schedule for weekly paclitaxel with 3 weekly trastuzumab *PRECAUTION: In order to reduce the risk of medication errors it is recommended that all trastuzumab products are referred to by brand name, i.e Herceptin IV CYCLE LENGTH AND NUMBER OF DAYS Three weekly (21 days). Loading dose of trastuzumab to be given on First day, and Palcitaxel the following day. On subsequent cycles when the risk of adverse reaction is lower the two treatments can be given on the same day. APPROVED INDICATIONS Advanced/ Metastatic breast cancer for patients whose tumours over-express human epidermal growth factor receptor 2 (HER2) EXCLUSION CRITERIA Herceptin is contraindicated in patients with severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy. Herceptin Paclitaxel_THREE_WEEKLY_CNTW_protocol_CRP09_B019_2.1 Page 1 of 5

2 ELIGIABILITY CRITERIA Should only be used in patients whose tumours have HER2 over-expression at a 3+ level as determined by immunohistochemistry (HER2 +++ by IHC or FISH) In combination with paclitaxel for the treatment of those patients who have not yet received chemotherapy for their metastatic disease and for whom an anthracycline is unsuitable. PREMEDICATION Premedication of dexamethasone, ranitidine and chlorpheniramine is given prior to Paclitaxel infusion to reduce of risk of hypersensitivity reaction. 3 weekly version: Dexamethasone can be given either as 20mg orally 12 and 6 hours prior to treatment or a 20mg IV bolus prior to treatment. Weekly version: Dexamethasone should be given as a 10mg IV bolus prior to treatment for weekly regimen RECOMMENDED TAKE HOME MEDICATION Metoclopramide 10 mg three times daily as required INVESTIGATIONS / MONITORING REQUIRED Paclitaxel Prior to each cycle - FBC, U/E s, LFT s as required BP and pulse to be monitored half hourly during paclitaxel infusion Herceptin Pre treatment During infusion HER2 test. Cardiac assessment incl. history and physical exam (esp. in those with prior AC exposure), ECG, Echocardiogram +/- MUGA Observe for fevers and chills or other infusion-related symptoms for at least 6 hours after the start of the first infusion, and for 2 hours after the start of subsequent infusions 3 to 4 monthly Cardiac function (ECHO/MUGA) ASSESSMENT OF RESPONSE Metastatic: Tumour size and patient symptomatic response REVIEW BY CLINICIAN To be reviewed by either a Nurse, Pharmacist or Clinician before every cycle. NURSE / PHARMACIST LED REVIEW On cycles where not seen by clinician. Herceptin Paclitaxel_THREE_WEEKLY_CNTW_protocol_CRP09_B019_2.1 Page 2 of 5

3 ADMINISTRATION NOTES Paclitaxel must be administered via a non-pvc administration set May not need to stop treatment for minor hypersensitivity e.g. reactions, flushing, localised rash. Must be stopped for major reactions, e.g. hypotension, dyspnoea, angioedema or generalised urticaria. If patient has hypersensitivity reaction follow manufacturers re-challenge guidelines before continuing with treatment. Units administering Paclitaxel and trastuzumab must have facilities available for the treatment of anaphylaxis and resuscitation. May not need to stop treatment for minor hypersensitivity e.g. reactions, flushing, localised rash. Must be stopped for major reactions, e.g. hypotension, dyspnoea, angioedema or generalised urticaria. Paracetamol can be used to treat reactions. Patients should be observed for 6 hours after the first dose of trastuzumab. EXTRAVASATION See NECN/ Local Policy Paclitaxel is a vesicant; therefore extreme care must be taken when infusion pumps are used to control rate of administration. The injection site must be regularly monitored during infusion. TOXICITIES Risk of hypersensitivity and anaphylaxis, particularly on first and second cycle, start within a few minutes of administration Pulmonary events, such as dyspnoea, bronchospasm, asthma and hypoxia. Adult Respiratory Distress Syndrome (ARDS) has been reported rarely with fatal outcome Cardiotoxicity - Do not give with anthracycline or give anthracycline within six months of patient receiving last dose of Herceptin. Hypotension and bradycardia Myelosupression, particularly, thrombocytopenia, anaemia & neutropenia Alopecia Peripheral neuropathy Myalgia Back pain on administration Diarrhoea, nausea, vomiting DOSE MODIFICATION / TREATMENT DELAYS Haematological Toxicity: Delay 1 week if WBC<3.0, ANC <1.0 Platelets <100 No dose modification for CTC grade I/II ANC Grade III/IV ANC delay chemotherapy until recovered. On recovery give 20% dose reduction Non- Haematological Toxicity: If PS deteriorates to Grade 3 or 4 and on assessment patient is more symptomatic withhold treatment and discuss with Oncologist Herceptin Paclitaxel_THREE_WEEKLY_CNTW_protocol_CRP09_B019_2.1 Page 3 of 5

4 Cardiac Toxicity The NECN Breast Guidelines give detailed guidance on management and monitoring of cardiac function during trastuzumab therapy. Available at Navigation through the guidelines may be facilitated by the adoption of a traffic light system summarised below. LVEF Monitoring At least 4 monthly for adjuvant patients, metastatic patients can be monitored less frequently (see breast guidelines for details) TREATMENT LOCATION Can be given at Cancer Centre or Cancer Unit REFERENCES: Verma S, Leyland-Jones B, Ayoub J-P et al. (2001) Efficacy and safety of threeweekly herceptin with paclitaxel in women with HER2-positive metastatic breast cancer: pre-liminary results of a phase ll trial. Eur J Cancer. 37 (Supplement 6): S146. Peretz T, Sulkes A, Chollet P et al (1999) A multicenter, randomized study of two schedules of paclitaxel (PXT) in patients with advanced breast cancer.(abc) Eur J Cancer. 31A (Supplement 5): S75. Seidman AD, Hudis CA, Albanel J et al. (1998) Dose-dense therapy with weekly 1-hour paclitaxel infusions in the treatment of metastatic breast cancer. J Clin Oncol. 16: Herceptin Paclitaxel_THREE_WEEKLY_CNTW_protocol_CRP09_B019_2.1 Page 4 of 5

5 Document Control Document Title: Herceptin & Paclitaxel THREE WEEKLY CNTW protocol CRP09 B019.doc Document No: Author: Approved by: CRP09 B019 Due for Review: 29 May 2016 Steve Williamson, Consultant Cancer Pharmacist Area Team Calum Polwart, Area Team Cancer Pharmacist Current Version: Approval Signature* Date Approved: Summary of Changes 1.1 Reformatted from old NCN/CCA version May 2014 Change to brand name following 2014 safety warning. Update cardiac monitor in line with other protocols 2.1` Protocol reviewed and reissued, Antiemetic advice updated Herceptin Paclitaxel_THREE_WEEKLY_CNTW_protocol_CRP09_B019_2.1 Page 5 of 5