PHRM 542 Oncology Supportive Care VTE, Cardiotoxicity, Infertility, Mucositis

How does cancer increase VTE risk?

Malignant cells can secrete pro coagulants or stimulate the immune system to secrete cytokines

What are VTE risk factors in cancer?

Active cancers associated with high incidence of VTE

BMI ≥ 35 kg/m^2

Prior VTE

Prechemotherapy platelet count > 350,000/mcL

Prechemotherapy WBC > 11,000/mcL

Prechemotherapy hemoglobin < 10 g/dL

Use of erythropoiesis stimulating agents (ESAs)

Which patients should be considered for VTE prophylaxis PRIOR to starting therapy?

High risk patients

When should patients be considered for VTE prophylaxis?

Khorana score ≥ 2 should consider anticoagulant prophylaxis for up to 6 months or longer

What is the standard dose of dalteparin for VTE prophylaxis (inpatient)?

5000 units SC daily

When should dalteparin be avoided?

CrCl < 30 mL/min

What is the standard dosing of enoxaparin for VTE prophylaxis (inpatient)?

40 mg SC daily

What is the renal dose adjustment of enoxaparin for VTE prophylaxis?

30 mg SC daily if CrCl < 30 mL/min

What is the standard dosing of fondaparinux for VTE prophylaxis?

2.5 mg SC daily

When should fondaparinux be used with caution and avoided?

Use with caution if CrCl 30-49 mL/min

Avoid if CrCl < 30 mL/min

What is the standard dosing of UFH for VTE prophylaxis?

5000 units SC every 8-12 hours

What is the standard dosing of apixaban for VTE prophylaxis in oncology patients?

2.5 mg PO twice daily

What is the standard dosing of rivaroxaban for VTE prophylaxis in oncology patients?

10 mg PO once daily

What is the standard dosing of dalteparin (outpatient)?

200 units/kg SC daily x 1 month

THEN

150 units/kg SC daily x 2 months

What is the standard dosing of enoxaparin for VTE prophylaxis (outpatient)?

1 mg/kg SC daily x 3 months

THEN

40 mg SC daily

With what CrCl should apixaban, rivaroxaban, dalteparin, and enoxaparin be avoided outpatient?

CrCl < 30 mL/min

How long should cancer patients be treated with anticoagulation for VTE?

At least 3 months or if active cancer remains or cancer therapy continues

When are DOACs preferred for VTE treatment in cancer patients?

First line agent for patients WITHOUT gastric or gastroesophageal lesions

How should edoxaban be initiated?

Initiate LMWH or UFH for 5 days prior to edoxaban

When are LMWHs preferred for VTE treatment in cancer patients?

First line agent for patients WITH gastric or gastroesophageal lesions

When can fondaparinux be used for VTE treatment in cancer patients?

Can use for heparin-induced thrombocytopenia

What is required when administering warfarin for VTE treatment in cancer patients?

Bridging

Define type I cardiotoxicity

Caused by cardiomyocyte death

Not reversible

Describe acute type I cardiotoxicity

Immediate onset after single dose/course of therapy with anthracycline

Describe chronic type I cardiotoxicity

Onset usually within 1 year of receiving anthracycline

Related to cumulative dose

Describe late onset type I cardiotoxicity

Develops several years or decades after therapy

Most common in childhood & adolescent cancer survivors

Describe type II cardiotoxicity

Caused by cardiomyocyte dysfunction (no direct damage)

Appears to be reversible & short-lived once agent stopped

NOT dose-related

What non-anthracycline drug classes are known to cause cardiotoxicity?

Microtubule targeting

Alkylating agents

Antitumor antibodies

Monoclonal antibodies

Protein kinase inhibitors

Others

What are risk factors for cardiotoxicity with anthracyclines?

Age > 65 years or < 4 years

Female gender

Hypertension

Preexisting cardiac disease

Mediastinal radiation

Higher individual anthracycline doses

Bolus dosing

Cumulative anthracycline doses

How can anthracycline cardiotoxicity be prevented?

Dexrazoxane for patients who have received 300 mg/m^2 of doxorubicin (10:1 ratio)

How do cytotoxic agents affect female gonadal function?

Affect the granulose and theca cells of the ovary more than the nondividing oocytes

How do cytotoxic agents affect male gonadal function?

Affects spermatogenesis > testosterone production

Degree of damage of germinal cell greater after puberty

Effect is both drug specific and dose dependent

What are risk factors to developing chemotherapy-induced mucositis?

Poor oral hygiene

Tobacco/alcohol

Female > male

Nutritional status

What types of chemotherapeutic agents are more stomatoxic?

DNA cycle specific are more stomatoxic than those that are cell phase nonspecific

How can chemotherapy-induced mucositis be prevented?

Good oral hygiene

MTOR inhibitors = dexamethasone rinse swish and spit

Oral cryotherapy

Palifermin

How can chemotherapy-induced mucositis be treated?

Supportive management

Anti-infectives

What is the onset of chemotherapy-induced mucositis?

5-10 days

What is the duration of chemotherapy-induced mucositis?

1-6 weeks