Thames Valley Thames Valley Chemotherapy Regimens Rare Tumours Thames Valley Notes from the editor These regimens are available on the Network website www.tvscn.nhs.uk. Any correspondence about the regimens should be addressed to: Sally Coutts, Cancer Pharmacist, Thames Valley email: [email protected] Tel: 01865 857158 to leave a message Acknowledgements These regimens have been compiled by the network pharmacy group in collaboration with the Chemotherapy Cross Cutting Group Andrew Weaver, Consultant Oncologist, OUH Denis Talbot, Consultant Medical Oncologist, OUH Paul Rogers, Consultant Oncologist, RBFT © Thames Valley Cancer Network. All rights reserved. Not to be reproduced in whole or part without permission of the copyright owner. Chemotherapy RegimenRegimens – Rare Cancers 2 of 44 Thames Valley Thames Valley Chemotherapy Regimens Rare Tumours Network chemotherapy regimens used in the management of Rare Tumours or are rarely used regimens All regimens in this document must include references and do not come under the remit of a particular PODG. Date published: October 2015 Date of review: October 2017 Chemotherapy regimens Name of regimen Indication Page List of amendments in this version 4 Mitotane Metastatic adrenal cancer 5 Everolimus Neuroendocrine 7 Streptozocin & Modified De Gramont Neuroendocrine 9 Streptozocin & Capecitabine Neuroendocrine 11 Streptozocin/ Cisplatin/ 5FU (FCiSt) Neuroendocrine 13 inpatient Sunitinib Neuroendocrine 16 Temozolomide & Capecitabine Neuroendocrine 18 Capecitabine Neuroendocrine, Carcinoid tumour 20 Cisplatin & Etoposide Neuroendocrine, Thymoma 22 Doxorubicin/ Cisplatin/ Vincristine/ Thymoma 24 cylophosphamide (ADOC) Cyclophosphamide, Vincristine and Thymoma, Thyroid cancer, 26 Dacarbazine (CVD) Cabozantinib Thyroid cancer Doxorubicin (Thyroid) Thyroid cancer 28 Sorafenib Thyroid cancer 29 Vandetanib Thyroid cancer 31 5-FU/ Cyclophosphamide/ Parathyroid carcinoma 33 Dacarbazine Doxorubicin/ Cisplatin/ Etoposide Adrenal gland 35 (EDP) Cisplatin, Methotrexate and Metastatic penile cancer 37 Bleomycin (PMB) Pre and post-hydration regimen 39 Common Toxicity Criteria 40 Chemotherapy RegimenRegimens – Rare Cancers 3 of 44 Thames Valley List of amendments in this version Regimen type: Rare Tumours Date due for review: October 2017 Previous Version number: 2.3 This version number: 2.4 Table 1 Amendments Page Action Amendment Made/ Type asked by Table 2 New regimens to be approved and checked included in this version Name of regimen Indication Reason / Proposer Cabozantinib Thyroid CDF Chemotherapy RegimenRegimens – Rare Cancers 4 of 44 Thames Valley Mitotane (Lysodren) Indication: the treatment of inoperable metastatic adrenal cortical carcinoma of both functional and nonfunctional types, neuroendocrine tumors DRUG REGIMEN The recommended treatment schedule is to start the patient at 2 to 6 g of mitotane per day in divided doses, either three or four times a day. Doses are usually increased incrementally to 9 to 10 g per day. (mitotane is available as 500 mg scored tablets) Treatment should be continued as long as clinical benefits are observed. Maintenance of clinical status or slowing of growth of metastatic lesions can be considered clinical benefits if they can clearly be shown to have occurred. If no clinical benefits are observed after 3 months at the maximum tolerated dose, the case would generally be considered a clinical failure. However, 10% of the patients who showed a measurable response required more than 3 months at the MTD. A number of patients have been treated intermittently with treatment being restarted when severe symptoms have reappeared. Patients often do not respond after the third or fourth such course. Experience accumulated to date suggests that continuous treatment with the maximum possible dosage of mitotane is the best approach DOSE MODIFICATIONS If severe side effects appear, the dose should be reduced until the maximum tolerated dose is achieved. If the patient can tolerate higher doses and improved clinical response appears possible, the dose should be increased until adverse reactions interfere. Experience has shown that the maximum tolerated dose (MTD) will vary from 2 to 16 g per day, but has usually been 9 to 10 g per day. The highest doses used in the studies to date were 18 to 19 g per day. MISSED DOSES: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not "double- up" the dose to catch up. INVESTIGATIONS Routine Blood test as required Creatinine clearance (GFR) calculated or EDTA at the Consultants discretion LFTs Mitotane levels [patients at ORH are sent to Baggot & Drake ward in OCDEM with appropriate biochemistry form – blood is spun down and sent to France for analysis. Usually takes at least 14 days to get result back]. Urine pregnancy test in women aged 12-55, unless sterilised or undergone a hysterectomy. Mitotane Clinical Group Chair Authorisation: Page 1 of 2 Published: October 2015 Version Date 2.4 Review: October 2017 Chemotherapy RegimenRegimens – Rare Cancers 5 of 44 Thames Valley CONCURRENT MEDICATION Mitotane has been reported to accelerate the metabolism of warfarin by the mechanism of hepatic microsomal enzyme induction, leading to an increase in dosage requirements for warfarin. Therefore, closely monitor patients for a change in anticoagulant dosage requirements when administering mitotane to patients on coumarin-type anticoagulants. In addition, mitotane should be given with caution to patients receiving other drugs susceptible to the influence of hepatic enzyme induction. ADVERSE EFFECTS / REGIMEN SPECIFIC COMPLICATIONS A very high percentage of patients treated with LYSODREN have shown at least one type of side effect. The main types of adverse reactions consist of the following: Gastrointestinal disturbances, which consist of anorexia, nausea or vomiting, and in some cases diarrhea occur in about 80% of the patients. Central Nervous System side effects occur in 40% of the patients. These consist primarily of depression as manifested by lethargy and somnolence (25%), and dizziness or vertigo (15%). Skin toxicity has been observed in about 15% of the cases. These skin changes consist primarily of transient skin rashes which do not seem to be dose related. In some instances, this side effect subsided while the patients were maintained on the drug without a change of dose. Infrequently occurring side effects involve the eye (visual blurring, diplopia, lens opacity, toxic retinopathy); the genitourinary system (hematuria, hemorrhagic cystitis, and albuminuria); cardiovascular system (hypertension, orthostatic hypotention, and flushing); and some miscellaneous effects including generalized aching, hyperpyrexia. patient info sheets and drug characteristics on the Lysodren website : http://www.lysodren- europe.com/index.aspx REFERENCES 1. Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs. NIH Publication No. 83-2621. For sale by the Superintendent of Documents, US Government Printing Office, Washington, DC 20402. 2. AMA Council Report. Guidelines for Handling Parenteral Antineoplastics. JAMA 1985; 253(11)1590-1592. 3. National Study Commission on Cytotoxic Exposure Recommendations for Handling Cytotoxic Agents. Available from Louis P. Jeffrey, ScD, Chairman, National Study Commission on Cytotoxic Exposure, Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, Massachusetts 02115. 4. Clinical Oncological Society of Australia: Guidelines and Recommendations for Safe Handling of Antineoplastic Agents. Med J Australia 1983; 1:426-428. 5. Jones, RB, et al: Safe Handling of Chemotherapeutic Agents: A Report from the Mount Sinai Medical Center. CA A Cancer Journal for Clinicians 1983; (Sept/Oct) 258-263. 6. American Society of Hospital Pharmacists Technical Assistance Bulletin on Handling Cytotoxic Drugs in Hospitals. Am J Hosp Pharm 1990; 47:1033-1049. 7. Controlling Occupational Exposure to Hazardous Drugs. (OSHA Work-Practice Guidelines). Am J Health-Syst Pharm 1996;53:1669-1685. 8. Fassnacht M et al Combination chemotherapy in advanced adrenocortical carcinoma. NEJM 366;23 nejm.2190 org june 7, 2012 Mitotane Clinical Group Chair Authorisation: Page 2 of 2 Published: October 2015 Version Date 2.4 Review: October 2017 Chemotherapy RegimenRegimens – Rare Cancers 6 of 44 Thames Valley Everolimus Indication: Pancreatic neuroendocrine tumour 2nd line Ensure funding is available for patient prior to prescribing. DRUG REGIMEN Day 1 Everolimus 10mg orally daily Cycle Frequency: Daily for 4 weeks continuously until progression DOSE MODIFICATIONS Everolimus: Any dose modifications should be discussed with a Consultant. Renal impairment No dose adjustment is required in patients with renal impairment. Hepatic impairment For patients with moderate hepatic impairment (Child-Pugh class B), the dose should be reduced to 5 mg daily. Everolimus has not been evaluated in patients with severe hepatic impairment (Child-Pugh class C) and is not recommended for use in this patient population. INVESTIGATIONS Routine Blood test 1) Blood results required before drug administration Give Discuss Hb x g/dL ≥10 < 10 Plt x 109/L ≥100 < 100 Neutrophils x 109/L ≥1.5 < 1.5 Routine bloods: FBC, renal function, liver function. Random blood sugar, lipid profile; if elevated to repeat on fasting blood Baseline imaging: CT and/or MRI at baseline and every three months. 2) Non urgent tests Tests relating