MANAGEMENT OF TREATMENT RELATED SIDE-EFFECTS: SYSTEMIC AND RADIATION

THERAPY

Charmaine Lynden NP; Cindy Quinton MD, FRCPC; Sarah Rauth MD, FRCPC

Faculty: Dr. MD, with the Mississauga Halton/Central West Regional Cancer Program: “Primary Care Oncology Day” Relationship with Commercial Interests: No affiliation (financial or otherwise) with a pharmaceutical, medical device or communications organization.

Faculty/Presenter Disclosure

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Quinton and Rauth

Objectives

• Recognize potential and expected side effects of radiation and systemic therapy

• Learn to manage treatment related side effects • Discover available resources

Case Study – Mrs. A

• 60 yo female• OBSP• Mammogram• Biopsy – DAU• Surgery – Lumpectomy

and Sentinel Lymph node• Pathology: pT2pN0M0• Receptor positive, HER 2

positive

Case Study

What would be an expected post-operative complication you would potentially see in your practice?

A. Seroma B. Cellulitis C. Hematoma D. All of the above

Post-operative Complications

• SEROMA– Collection of fluid in potential

space– No intervention necessary

• CELLULITIS– Painful, warm, erythematous– Can have fever, chills and rigors– Treat:

• Pain control• Antibiotics (Keflex)• If no improvement in 48-72

hours involve surgeon

Case Study

• Mrs. A presents to her family physician 2 weeks post-operatively complaining of a large swollen breast. It ispainful and tender to touch, however, she is afebrileand there are no erythematous changes to her skin.As her family physician you are concerned she hasdeveloped a post-operative seroma. What would beyour next steps?A. Observation and F/U in one week B. Ultrasound C. Contact surgeon

Radiotherapy

• Radiotherapy Timing• Radiotherapy Dose

Side Effects of Radiation Depends On

• The area of the body beingtreated

• The size of the treatmentarea

• The dose of radiotherapyprescribed

• The fractionation oftreatment

• The general health of thepatient

• Previous or concurrentchemotherapy or surgery

Side Effects of Radiotherapy

• Skin reaction• Hair loss• Diarrhoea• Mucositis• Sterility• Frequency of passing urine• Fatigue• Anorexia• Psychological effects• Nausea and vomiting

Radiotherapy Side-Effects Acute - Fatigue

• GENERAL FATIGUE– physical (marrow suppression)– Emotional– Combined effect with co-morbid conditions– Occurs in 80% of patients during treatment– Occurs in 30% of patients after treatment

• MANAGEMENT OF FATIGUE– Identify and treat any functional causes eg. anemia– Physical activity– CBT – coping– Chemical – psychostimulants, dexamethasone (last choice)

Case Study

• Mrs. A returns to see her family physician 1 week aftercompleting her radiotherapy with a brisk skin reactionto her entire breast, with moist desquamation in theaxilla and inframammary fold.

• How would you manage this presentation?1. Observation2. Debridement3. Saline soak compresses4. Antibiotic ointment

Radiotherapy Side-Effects Acute Skin

• RADIATION DERMATITIS– Erythema– Swelling– Discomfort– Desquamation (Moist/Dry)– Worst about 7 days after XRT– Complete resolution 20-30

days after xrt– (re-epithelialization)

• TREATMENT– Saline soaks– Glaxol base, Polysporin,

(flamazine)– Analgesia– Loose clothes

Radiotherapy Side-Effects Late

• Hyperpigmentation, telengectasias of skin• Lymphedema• Fertility issues/sexual function• Second malignancy (younger than 60)• Chronic fatigue• Changes in bowel and bladder habit• Swallowing difficulties• Chronic nausea and vomiting• Increased shortness of breath

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Toxicities of Chemotherapy

• Nausea and Vomiting– Newer antiemetics – palonesetron, aprepitant

• Fatigue• “Chemo- fog”• Mucositis• Cardiac- ischemia, vasospasm, cardiomyopathy• Hand foot syndrome• Growth factor related pain• Taxane- related neuropathy, edema, pneumonitis• CCO SYMPTOM MANAGEMENT GUIDELINES

Case Study

Mrs. A starts on FEC- Docetaxel chemotherapy with a year of adjuvant Herceptin. What chemotherapy related side effects might Mrs. A experience?

A. Pain B. Vomiting C. Shortness of breath D. Fever

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Download the free app on your mobile device: Apple iOS ; Android ; Windows Phone

Use the app on your computer: smg.cancercare.on.ca

HAND FOOT SYNDROME

Taxane induced pneumonitis

Case Study – Mrs. A

After completing chemotherapy Mrs. A starts on her hormonal therapy with Anastrozole (Arimidex) an aromatase inhibitor. What are the expected side effects Mrs. A may experience?

A. Pain B. Hot flashes C. Dyspareunia D. Insomnia

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Toxicities of Targeted Agents

• Trastuzumab: reduction in LVEF, reversible

• Anti VEGF- agents: hypertension• Bevacizumab-perforation, proteinuria• Sunitinib- cardiac impairment, nephrotic syndrome, pancreatitis

• TDM-1: trastuzumab emtansine (DRUG-ANTIBODY CONJUGATE)• LVEF, myelosuppression, hepatotoxicity, neuropathy

• EGFR- inhibitors: erlotinib, gefitinib, panitumumab, cetuximab RASH – clindamycin lotion, hydrocortisone cream, oral clindamycin DIARRHOEA- immodium

Selected adverse events (% of patients)

Vemurafenib, n=337 Dacarbazine, n=287 Adverse events All Grade 3 Grade ≥4 All Grade 3 Grade ≥4

Arthralgia 56 6 – 4 1 –

Rash 41 9 – 2 – –

Fatigue 46 3 – 35 2 –

Photosensitivity 41 4 – 5 – –

↑LFTs 26 10 1 6 2 –

Cutaneous SCC 19 19 – <1 <1 –

Keratoacanthoma 11 10 – <1 <1 –

Skin papilloma 28 <1 – <1 <1 –

Nausea 38 2 – 45 2 –

Neutropenia <1 – <1 12 6 3 Discontinuations due to AE: 7% vemurafenib; 2% dacarbazine

8 patients reported new primary melanomas in the vemurafenib group

Ipilimumab irAEs Requiring Immediate Treatment

Immune-related adverse events that should be addressed

immediately:

• Diarrhea, blood in stool, constipation, fever

• Headache, visual-field defects, fatigue/weakness, coma

• Muscle weakness

• Elevations in liver function tests (eg, AST, ALT,

total bilirubin) in the absence of clinical symptoms

ALT: alanine aminotransferase AST: aspartate aminotransferase GI: gastrointestinal irAE: immune-related adverse event

• Liver function tests, thyroid function tests, and electrolytes should beevaluated at baseline and before each dose of ipilimumab

• Monitor patients for signs and symptoms indicative of immune-relatedadverse reactions including, but not limited to:

Monitoring and Laboratory Tests

• ↑ Transaminase and bilirubin levels• Eye pain and visual disturbances• Mental status changes• Sensory alterations• Hypotension• Paresthesia• Muscle weakness (unilateral or bilateral)• Headache• Fatigue

• ↑ Frequency of bowel movements• Diarrhea• Mucus or blood in stool with or without fever• Unusual bowel habits• Peritoneal signs• Abdominal pain• Ileus• Pruritus• Rash

Combined Modality Treatment

Concurrent Chemotherapy and Radiotherapy

• Provides more activity on tumour cells resulting in a greaterdegree of cell death

• Effectiveness of treatment is increased• Often used for locally advanced, un-resectable solid tumours or

neo-adjuvantly• Radiosensitizers – 5-FU or Xeloda, Cisplatinum

• Chemical or pharmacologic agent which increases radiationdamage to sensitive cells when given in combination withradiation

• Given to enhance damage to tumor cells while minimizingtoxicities to normal tissue

Rationale for Using Combined Modalities

• Improve:o outcomeso overall survivalo loco-regional controlo quality of lifeo functional status

Combined Modality Protocols At PRCC

• Stage III A/B NSCLC• Limited stage SCLC• GI

o Rectalo Gastrico Esophageal

• Pancreatic• Anal canal• Gynaecological (cervix only)

Treatment Related Toxicities

• Toxicities can be increased with concurrent protocols• NCIC grading system• Most common

o Skin reactions (moist desquamation)o Nausea and vomittingo Esophagitiso Diarrheao Fatigue

Skin Reactions

• Prevent or minimizeo Application of Cavilon No-Sting barrier twice/week at the

start of treatment• Treatment

o Comfort measureso Saline soak compresseso Loose fit clothingo Mild soapo Flamazineo opiods

Radiation Dermatitis

Radiation Dermatitis

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Radiation Esophagitis

• Usually occurs 2-3 weeks into radiation treatment• >50Gy and volume of esophagus receiving treatment• More common in concurrent

Chemotherapy and radiation(CCRT)

Radiation Esophagitis

• A Radiation Therapy Oncology Group (RTOG) analysis found thatconcurrent chemotherapy increases the risk of esophagitis 12 fold

• CCRT was significantly associated with a risk of Grade 3-5 esophagealtoxicity

Clinical Manifestations

• Dysphagia• Odynophagia• Pain• Substernal discomfort• Esophageal fistula

o Wet cougho Empyema

Treatment

• Radiation Esophagitis Drinko (lydocaine, nystatin and fruit drink)

• Opiods• Diet modification

o Bland, soft or pureeo Smoothies

• Tracheo-esophageal fistula (TEF)o stent

Radiation Proctitis

• Approximately 75% of patients who receive pelvicradiation >50Gy

• More common in concurrent protocols• Acute or chronic

Radiation Proctitis

Pale mucosa and telangiectasis Ulceration, bleeding and fibrosis

Radiation Proctitis

Acute • Begins 3rd week of

treatment and may lastseveral weeks followingtreatment

Chronic • Can occur months to year

following XRT• Impacts quality of life

Clinical Manifestations

Acute • Diarrhea• Tenesmus• Mucous discharge• Abdominal and rectal pain• Bleeding (less common)

Chronic • Diarrhea• Mucous discharge• Fistula• Tenesmus• Pain• Urgency• Incontinence

Treatment

• Focused on symptom management• Steroidal enemas or suppositories• Pain medication• Imodium or Lomotil• Alter diet

Resources

• Feel free to contact the Oncology health care team if youhave any questions or concerns regarding treatmentrelated side effects.

• Cancer Care Ontario - https://www.cancercare.on.ca/• PDQ –

o www.cancer.gov/cancertopics/pdq