7.1 Oncology & Support Care

Oncology & Support Care

Oncology pharmacy practice requires an intricate understanding of chemotherapy toxicity mitigation and the management of supportive care complications. The clinical pharmacist plays a vital role in interpreting risk models, adjusting antiemetic regimens, managing end-organ toxicities, and rapidly addressing oncologic emergencies.

Chemotherapy Toxicity Risk: The CARG Score

Evaluating the risk of chemotherapy-associated toxicity in older adults (≥ 65 years) cannot rely on chronological age alone. The Cancer and Aging Research Group (CARG) score is a validated tool designed to predict the risk of grade 3-5 toxicity in older patients receiving chemotherapy. A higher score correlates with an increased likelihood of severe adverse events.

CARG Score Risk Factors

• Patient Characteristics: Age ≥ 72 years.
• Tumor/Treatment: Gastrointestinal or genitourinary cancer, receiving standard-dose chemotherapy (as opposed to reduced dose), and receiving a multi-agent regimen.
• Laboratory Values: Decreased creatinine clearance (< 34 mL/min) and anemia (Hemoglobin < 11 g/dL for males or < 10 g/dL for females).
• Geriatric Assessment Variables: Polypharmacy (≥ 5 daily medications), dependency in instrumental activities of daily living (IADLs), one or more falls in the last 6 months, and decreased physical performance (e.g., needing assistance walking 1 block).

Based on the cumulative score, patients are stratified into low, intermediate, or high risk for toxicity. Pharmacists utilize this score to recommend pre-emptive dose reductions or to switch to less toxic alternative regimens.

Specific Chemotherapy Toxicities

Understanding class-specific adverse effects is paramount. The clinical pharmacist must monitor cumulative lifetime doses and administer appropriate chemoprotectants.

• Anthracyclines (Doxorubicin, Epirubicin): Notorious for irreversible, cumulative cardiotoxicity (dilated cardiomyopathy). The lifetime maximum cumulative dose for doxorubicin is typically capped at 450–550 mg/m². The iron-chelating agent Dexrazoxane (Zinecard) can be used as a cardioprotectant to prevent free radical damage in high-risk patients.
• Bleomycin: Associated with severe, dose-limiting pulmonary fibrosis. The lifetime maximum dose is 400 units. Patients require baseline and routine pulmonary function tests (PFTs), specifically monitoring the diffusing capacity of the lungs for carbon monoxide (DLCO). Supplemental oxygen can exacerbate bleomycin pulmonary toxicity.
• Platinum Analogs:
  • Cisplatin is highly emetogenic and causes severe nephrotoxicity and ototoxicity. It mandates vigorous pre- and post-hydration with normal saline. Amifostine (Ethyol) may be administered prophylactically to reduce renal toxicity.
  • Oxaliplatin uniquely causes acute cold-induced sensory neuropathy (exacerbated by cold temperatures or cold drinks) and persistent peripheral neuropathy.
• Vinca Alkaloids (Vincristine, Vinblastine): Associated with severe peripheral neuropathy and autonomic neuropathy (e.g., paralytic ileus). Vincristine doses are often strictly capped at 2 mg per dose, regardless of body surface area, to prevent permanent neurologic damage. Crucial: Vinca alkaloids are fatal if administered intrathecally.
• Alkylating Agents (Cyclophosphamide, Ifosfamide): Can cause hemorrhagic cystitis due to the accumulation of the toxic metabolite acrolein in the bladder. Prevention requires vigorous hydration and co-administration of Mesna (Mesnex), which binds and inactivates acrolein.
• Taxanes (Paclitaxel, Docetaxel): Associated with significant hypersensitivity reactions (due to solvents like Cremophor EL) and peripheral neuropathy. Strict pre-medication regimens including dexamethasone, diphenhydramine, and H2-blockers are required prior to administration.

Febrile Neutropenia (FN)

Febrile neutropenia is an oncologic emergency requiring rapid intervention. It is defined as a single oral temperature of ≥ 38.3°C (101°F) or a temperature of ≥ 38.0°C (100.4°F) sustained over 1 hour, alongside an Absolute Neutrophil Count (ANC) < 500 cells/mm³, or an ANC expected to decrease to < 500 cells/mm³ within 48 hours.

Empiric Antimicrobial Therapy

The cornerstone of FN management is the prompt initiation of an intravenous antipseudomonal beta-lactam.

• First-line agents: Cefepime, Piperacillin-Tazobactam, or Meropenem/Imipenem-Cilastatin.
• Outpatient management: For low-risk patients (MASCC score ≥ 21), oral therapy with a fluoroquinolone (Ciprofloxacin or Levofloxacin) plus Amoxicillin-Clavulanate may be appropriate.

Indications for Adding Vancomycin

Routine empiric use of Vancomycin is NOT recommended due to the risk of resistance and nephrotoxicity. It should only be added for specific indications:

• Hemodynamic instability or severe sepsis/septic shock.
• Radiographically confirmed pneumonia.
• Positive blood cultures for Gram-positive bacteria before final identification.
• Suspected catheter-related infection.
• Skin/soft tissue infection.
• Known colonization with MRSA, VRE, or penicillin-resistant pneumococci.

If cultures remain negative after 48-72 hours and the patient is stable, Vancomycin should be discontinued to prevent excess toxicity.

Chemotherapy-Induced Nausea and Vomiting (CINV)

CINV prevention relies on targeting multiple neurotransmitter pathways (serotonin, substance P, dopamine) before the emetogenic stimulus begins. Regimens are tailored to the emetogenic potential of the chemotherapy protocol.

Emetogenic Risk Categories & Prophylaxis

Note on Olanzapine: Commonly dosed at 5-10 mg PO daily for 4 days. Caution in elderly patients due to oversedation and anticholinergic effects. Breakthrough CINV: Utilize an agent from a different pharmacological class than the prophylactic regimen (e.g., Metoclopramide, Promethazine, Haloperidol, or Cannabinoids).

Oncologic Emergencies

Tumor Lysis Syndrome (TLS)

TLS is a massive release of intracellular contents resulting from the rapid lysis of malignant cells, typically seen in bulky, rapidly proliferating tumors like leukemias and lymphomas (e.g., Burkitt lymphoma) after initiating cytotoxic therapy. The precipitation of uric acid and calcium-phosphate crystals in the renal tubules leads to acute uric acid nephropathy and acute kidney injury.

Metabolic Hallmarks of TLS:

• Hyperuricemia: Released purines are metabolized to uric acid.
• Hyperkalemia: Rapid release of intracellular potassium.
• Hyperphosphatemia: Release of intracellular phosphate, which then binds to calcium.
• Hypocalcemia: Secondary to precipitation with phosphate.

Management:

1. Aggressive IV Hydration: Normal saline to maintain high urine output and prevent uric acid/calcium-phosphate precipitation.
2. Allopurinol: A xanthine oxidase inhibitor used for prophylaxis to prevent the formation of new uric acid. It does not reduce existing uric acid levels. Requires dose adjustments in renal impairment.
3. Rasburicase: A recombinant urate oxidase enzyme that actively converts existing uric acid into allantoin (a highly soluble compound). Used for treatment of established hyperuricemia or high-risk TLS. Absolute contraindication: G6PD deficiency due to the risk of severe hemolytic anemia.

Hypercalcemia of Malignancy

Often mediated by parathyroid hormone-related protein (PTHrP) secreted by squamous cell lung cancers, renal cancers, and breast cancers, or by direct osteolytic bone metastases.

Management:

• Mild (< 12 mg/dL): Oral hydration and observation.
• Moderate to Severe (≥ 12 mg/dL or symptomatic):
  • Immediate: Aggressive IV normal saline hydration to promote renal excretion of calcium.
  • Short-term: Calcitonin (rapid onset within hours, but tachyphylaxis develops after 48 hours of use). Limits its utility beyond the initial acute phase.
  • Long-term: IV Bisphosphonates (Zoledronic acid 4 mg IV or Pamidronate) which take 24-72 hours to reach maximal effect. Denosumab (Xgeva), a RANKL inhibitor, is an alternative for refractory hypercalcemia or severe renal impairment (as bisphosphonates are intrinsically nephrotoxic).