Managing Chemotherapy Toxicities in GI Cancers

Managing Chemotherapy Toxicities in GI Cancers September 30, 2008 Christine Brezden-Masley, MD PhD FRCPC

To understand toxicities from colorectal cancer therapy gastric cancer therapy To manage toxicities from colorectal cancer therapy gastric cancer therapy Objectives

Adjuvant colorectal cancer FOLFOX Xeloda Clinical trial: CRC2 – Stage 3 CRC: FOLFOX +/- Cetuximab (for RAS wt patients) CRC3 – Stage 2 CRC: 18q deletion: FOLFOX +/- Avastin CRC4 – Stage 2-3 Rectal cancer: FOLFOX +/- Avastin Colorectal Cancer

Dose-limiting cold-induced sensory peripheral neuropathy Ask patients if are able to button shirt and write If so, but have tingling >14 days (into next cycle) then decrease dose of oxaliplatin 85 mg/m2 to 65 mg/m2 If pain and significant paresthesia, cannot button shirt, cannot write – discontinue oxaliplatin and continue with FUFA Any prevention studies for neuropathy? FOLFOX

CalMag Infusions

2008 ASCO

CalMag 2-3 tablets per day without food Stay warm Do not drink cold fluids Neuropathy

FOLFOX Hesketh 4 FOLFIRI Hesketh 4 ECF/ECX Hesketh 5 Xeloda (Capecitabine) Hesketh 2 Nausea and Vomiting

Immediate Zofran 8mg po BID Decadron 8 mg po BID X 3 days with chemotherapy Delayed Stemetil Maxeran Nausea and Vomiting

IV hydration at home CCAC daily IV hydration with NS 600ml/day Marinol/Nabilone (cannabinoid) Haldol Aprepitant Cost Zyprexa (olanzapine) Delayed N/V

FOLFOX FOLFIRI Imodium Loperamide NO MAXIMUM for chemotherapy-induced diarrhea Ensure no C.Difficile (ischemic gut) Somatostatin (100 mg sc x1) Diarrhea

Immediate diarrhea (during infusion) SN38 active metabolite Cholinergic response Treatment with Atropine 0.2 mg sc x1 Morphine (cramping) FOLFIRI

No role for primary prevention of GCSF FOLFIRI>FOLFOX ECF/ECX For CURATIVE intent Can treat with GCSF – funding an issue If private insurance – can use in advanced care to push doses Myelosuppression

If febrile neutropenia Not difficult for Section 8 to fund FOLFOX and Gemcitabine Thrombocytopenia If platelets <85 should dose-reduce Educate patient about bleeding risk Anemia Check for Fe stores – supplement Role for ESAs? Myelosuppression

Hand-Foot Syndrome Keep hands and feet moist with Udder cream May reduce dose if continues (blistering and desquamation and pain) Diarrhea Mucositis XELODA

Good oral hygeine critical Baking soda rinses – ½ teaspoon of baking soda in half glass of water daily 2-3x If severe neutropenia – than mucositis usually occurs Nystatin (Nilstat) 500,000 Units po q4-6 hours (swish and swallow) Tantum (ODB) Butlers/Blacksteins mouth wash Mucositis

Dihydropyrimidine dehydrogenase (DPD) Catabolic pathway of 5-FU Responsible for 85% of degradation of 5-FU 5-FU 5-FUTP 5-FdUMP (ACTIVE form) DPD deficiency 3-5% population (polymorphisms as high as 8%) Autosomal recessive DPD

DPD Deficiency Syndrome Grade 4 neutropenia Severe/fatal diarrhea Mucositis/stomatitis Rash Can happen after 1st or 2nd dose of 5-FU Treatment Supportive care DPD Deficiency

Shape your practice – you’re the boss Do not need to examine patient at each chemotherapy session – but need to MONITOR ALL BLOODWORK MONITOR SIDE-EFFECTS ASK PATIENT HOW THEY’RE DOING FATIGUE/ENERGY APPETITE MOOD Clinical Pearls

NEED TO ASSESS PATIENT Pain New symptoms/signs Dehydration Neurologic Major organ involvement Respiratory (r/o PE) Cardiac (electrolyte disturbances) Renal Hepatic (Ascites) CLINICAL PEARLS

Thanks Questions? brezdenc@smh.toronto.on.ca

Managing Chemotherapy Toxicities in GI Cancers