Exam 4 Review

Exam 4 Review Monday, April 07, 2025 12:06 AM BREAST CANCER • Stage up to 2 ○ Goal: cure, prevent, eradicate ○ All therapies okay • Stage 3 ○ Operable vs inoperable • Non-Invasive DCIS ○ Premenopausal – Tamoxifen +/- ovarian suppression ○ Postmenopausal – Tamoxifen or AI (advantage < 60 y/o or w/ thromboembolism) • Invasive Hormone (+) Premenopausal ER/PR+ Tamoxifen ± ovarian suppression • If clotting or VTE risk → AI (airomatase inhibitor) + ovarian suppression (GnRH agonists) ○ Airomatase Inhibitors: ▪ Anastrozole (Arimidex) ▪ Letrozole (Femara) ○ Ovarian Suppression (GnRH) ▪ Leuprolide (Lupron) ▪ Goserelin (Zoladex) ○ Postmenopausal ER/PR+ • AI x 5y • Tamoxifen 2-3 y + AI to complete 5 y (vice versa) • C/I to AI → Tamoxifen 5 y or consider 10 ▪ Monitor bone density • Recurrent or Stage IV HR(+)/HER2(-) • Pre/postmenopausal • 1st line: AI + CDK 4/6 inhibitor • Airomatase Inhibitors: • HR+/HER2○ Anastrozole (Arimidex) • Recurrent or Stage IV (metastatic) ○ Letrozole (Femara) ○ Exemestane (Aromasin) • CDK 4/6 inhibitors: ○ Palbociclib (Ibrance) ○ ○ Ribociclib (Kisqali) ○ Abemaciclib (Verzenio) • If progression or relapse within 12 months: ○ Fulvestrant + CDK 4/6 inhibitor • 2nd line: • Fulvestrant + CDK 4/6 inhibitor (if not used previously) • Everolimus + endocrine therapy (exemestane, fulvestrant, tamoxifen) • Recurrent or Stage IV HR(+/-)/HER2(+) ○ 1st-line: pertuzumab + trastuzumab + paclitaxel • Preoperative or Adjuvant Chemotherapy for HER2(-) ○ AC + paclitaxel • Preoperative or Adjuvant Chemotherapy for HER2(+) ○ Paclitaxel + trastuzumab • TNBC ○ Cytotoxic agents (chemotherapy) ▪ Anthracyclines – doxorubicin ▪ Nitrogen mustard – cyclophosphamide ▪ Platinum compounds – cisplatin ○ Target treatment – +/- PARP inhibitors (-parib) ○ Immune checkpoint inhibitor ▪ Pembrolizumab • KEYNOTE-522 regimen, a treatment for high-risk, early-stage triple-negative breast cancer (TNBC) • Bone Health ○ Zolendronic acid 4 mg IV q12 weeks – cancer-related ○ Xgeva 120 mg SQ q4 weeks – prevention (bone metastasis) ○ Prolia 60 mg SQ q6 months – treatment osteoporosis Osteoporosis Bone Metastasis AEs • Higher dose and/or intensity • OP & cancer doses • Cancer doses • Zoledronate (Reclast) • Zoledronate (generic) • Denosumab (Prolia) • Denosumab (Xgeva) • PO BPs • GI irritation • Both • Muscoskeletal – bone, joint, muscle pain • Hypocalcemia • Hypophosphatemia • Atypical sub-trochanteric fracture ○ "hip fractures" usually w/ trauma ○ Atypical – broken at shaft due to weight • Osteonecrosis of jaw (irreversible) • Denosumab • Increased risk of serious infections • Dermatologic –rash and eczema OVARIAN CANCER • Management of Ovarian Cancer ○ Platinum-based regimen ○ Cisplatin = carboplatin (few toxicities) • Early Stage (Stage 1 & 2) ○ Comprehensive surgical staging followed by: ▪ Stage 1 – taxane/liposomal doxorubicin + carboplatin 3-6 cycles ▪ Stage II – platinum based chemotherapy similar to stage III or IV • Advanced Stage (Stage III & IV) ○ Comprehensive surgical staging ○ 6 cycles taxane (paclitaxel or docetaxel) + platinum (carboplatin or cisplatin) ○ Stage III (patient-based) ▪ IP chemotherapy • Patient selection is CRITICAL! ○ Optimally debulked Patients ○ Younger (<65 y/o) ○ Good-Excellent PS (High KPS, Low ECOG) ▪ KPS (ability to function) ▪ ECOG: 0 – 5 • Low = healthy, active • High = disabled/deceased ○ Minimal to no comorbidities (renal, hepatic) → NO diabetes d/t increased neuro and nephrotoxicity ○ No significant bowel resection • Optimally debulked • Taxane + platinum every 3 weeks for 6 cycles CERVICAL CANCER • Testosterone use thins vaginal lining and decreases natural lubrication ▪ Can pretreat with 2 weeks of vaginal estrogen ▪ Use lots of lubrication and consider topical lidocaine • • PROSTATE CANCER • Asymptomatic Patients Prostate Screening ○ PSA +/- DRE • Normal range of total serum PSA is 0-4 ng/ml ○ 4-10 ng/mL equivocal ○ 10-20 ng/mL localized disease ○ >20 ng/mL extracapsular disease ○ >80 ng/mL widely metastatic ○ Can be based on age: ○ If 40-49 years old 0-2.5 ng/mL ○ If 50-59 years old 0-3.5 ng/mL ○ If 60-69 years old 0-4.5 ng/mL ○ If 70-79 years old 0-6.5 ng/mL • Treatment is based on risk of recurrence ○ Early therapies: RT or RP, ADT ○ Advanced or Metastatic: ADT, secondary hormonal therapies, chemotherapy, immunotherapy • Advanced/Metastatic Prostate Cancer ○ Surgery: orchiectomy ○ 1st line Hormone therapy: Androgen Deprivation Therapy (ADT) = GOLD STANDARD ○ LHRH=luteinizing hormone releasing hormone • All LHRH agonists ○ Biochemical tumor flare ○ GnRH=gonadotropin releasing hormone ▪ AEs ○ LNRH Agonist LNRH Antagonist • Leuprolide (Lupron, Eligard) • Goserlin (Zoladex) • Triptorelin (Trelstar) • Degarelix (Firmagon) • Relugolix (Orgovyx) • PO med approved Dec 2020 Tumor flare, loss of BMD, hot flashes, impotence, gynecomastia, bone pain, injection site pain, QT prolongation, dyslipidemia, hyperglycemia • Pretreat w/ antiandrogens for 7 days for symptoms of flare ↑ cardiovascular risk Hepatotoxicity NO tumor flare • ↓ in T on day 1 Dosage forms • Eligard – SQ injection • Zoladex – SQ implant • Lupron – IM Depot • Orgovyx – PO tablets • Firmagon – SQ injection ○ Pretreat: • First generation antiandrogens (prevent flare, got flashes) ○ Nilutamide (Nilandron) ○ Bicalutamide (Casodex) ○ Flutamide • 5-alpha reductase inhibitors ○ Finasteride (Proscar) ○ Dutasteride (Avodart) ○ Early Onset AEs of ADT ○ Erectile dysfunction → from orchiectomy or LHRH agonist/antagonist • Responds to phosphodiesterase inhibitors (Cialis) ○ Decreased libido → from orchiectomy or LHRH agonist/antagonist • Responds to testosterone supplementation. ○ Pain at injection site ○ Chemotherapy is reserved for patients who do not respond to ADT, or their disease progresses on ADT. ○ docetaxel, cabazitaxel, and mitoxantrone, or immunotherapy with sipuleucel-T • M0/M1 mCRPC + mCSPC ○ 2nd-generation antiandrogens ○ M0 CRPC or M1 CSPC • Enzalutamide • Apalutamide ○ M0 CRPC • Darolutamide ○ Androgen metabolism Inhibitor ○ M1 CRPC or CSPC • Abiraterone + prednisone (Zytiga) ○ Both resistant + sensitive ○ W/ food • Abiraterone + methylprednisolone (Yonsa) ○ FOR resistance only • Metastatic CRPC Summary ○ Consider sipuleucel-T in select patients (asymptomatic) ○ Docetaxel + Prednisone (NCCN category 1) • Benefit seen in patients with and without symptoms • Use for rapid disease progression or visceral metastases ○ Radium 223 • → Consider in symptomatic bone only disease • → Not used in combination with other chemotherapy ○ Abiraterone + Prednisone or Abiraterone + Methylprednisolone • Initial therapy if no visceral metastases (NCCN Category 1) ○ Enzalutamide (NCCN category 1) • No prednisone required • Initial therapy with or without visceral metastases ○ Cabazitaxel + Prednisone • After docetaxel • Has significant toxicities (myelosuppression, neuropathy) ○ Mitoxantrone + Prednisone • Use if patient is not a candidate for docetaxel ○ Myelosuppression ○ Peripheral neuropathy • No head to head comparison of initial therapies ○ Bone Metastasis • Summary • •