Is dapsone (diaphenylsulfone) used as a primary treatment for cancer?

Is Dapsone Used for Cancer?

No, dapsone is not used as a primary treatment for cancer itself, but it is extensively used in cancer patients as prophylaxis against Pneumocystis jirovecii pneumonia (PJP) and other opportunistic infections during immunosuppressive cancer therapy. 1

Primary Role in Cancer Care: Infection Prophylaxis

Dapsone serves as an alternative prophylactic agent when trimethoprim-sulfamethoxazole (TMP-SMX) cannot be tolerated in cancer patients at high risk for opportunistic infections. 1

Specific Cancer Populations Requiring PJP Prophylaxis

Category 1 Recommendations (Strongest Evidence):

• Allogeneic hematopoietic cell transplant (HCT) recipients: Prophylaxis for at least 6 months and while receiving immunosuppressive therapy 1
• Acute lymphoblastic leukemia (ALL) patients: Throughout antileukemic therapy 1

Category 2B Recommendations (Consider prophylaxis):

• Recipients of purine analog therapy and other T-cell-depleting agents until CD4 count >200 cells/mcL 1
• Autologous HCT recipients for 3-6 months post-transplant 1
• Patients receiving prolonged corticosteroids (≥20 mg prednisone equivalent daily for ≥4 weeks) 1
• Patients receiving temozolomide with radiation therapy 1
• Patients receiving select phosphatidylinositol-3-kinase inhibitors with rituximab 1

Dosing in Cancer Patients

Standard prophylactic dosing: 50-100 mg daily for both adults and children 1, 2

Alternative weekly dosing: 100-200 mg weekly, which demonstrated zero failure rate for primary prophylaxis and 8% recurrence for secondary prophylaxis in HIV patients 2

Critical Safety Concerns in Cancer Patients

Heightened Risk in Hematologic Malignancies

Cancer patients, particularly those with hematological malignancies, face significantly higher rates of dapsone-induced complications compared to other populations:

Oxidant Hemolysis:

• 87% incidence in stem cell transplant recipients with normal G6PD activity, compared to 0% with TMP-SMX 3
• This rate is 20-fold higher than reported in HIV-infected patients 3
• Manifests as lower hemoglobin levels, though typically not severe enough to require increased transfusions 3

Methemoglobinemia:

• 53% of cancer patients on dapsone who underwent co-oximetry testing showed elevated methemoglobin levels (≥1.5%) 4
• 20% of pediatric ALL patients developed symptomatic methemoglobinemia 5
• Mean onset occurs at 11.8 days (range 4-18 days) after starting dapsone 4
• Cancer patients become symptomatic at lower methemoglobin levels than healthy individuals due to underlying anemia 5, 4

Mandatory Pre-Treatment Screening

G6PD deficiency testing is required before initiating dapsone, as these patients are at particularly high risk for severe hemolysis 1, 2

Baseline laboratory monitoring should include: Complete blood count and liver function tests due to risks of hemolytic anemia, methemoglobinemia, neutropenia, and hepatotoxicity 2, 6

Drug Interactions in Cancer Patients

Azole antifungals (commonly prescribed in cancer patients) and high-dose corticosteroids induce cytochrome P-450 enzymes, potentiating dapsone toxicity 4

• In one audit, all patients who developed methemoglobinemia were on azole antifungals, and five were also on high-dose steroids 4
• Azoles should typically be held a minimum of 24 hours before through 24 hours after chemotherapy metabolized via CYP3A4 1

Monitoring Requirements

Frequent monitoring is essential in cancer patients receiving dapsone due to:

• Underlying anemia (mean hemoglobin 85.5 g/l in patients who developed methemoglobinemia) 4
• Immunosuppression 4
• Multiple potential drug interactions 1, 4

Routine co-oximetry testing enables early recognition of methemoglobinemia and may lessen the need for or duration of intensive care support 4

Special Populations

Patients with History of Malignancy and Hidradenitis Suppurativa

Dapsone is suggested as safe for systemic antibiotic use in patients with a history of malignancy who require treatment for hidradenitis suppurativa, as it is unlikely to be associated with increased risks based on its mechanism of action 1

HIV-Infected Cancer Patients

Dapsone provides added prophylactic benefit against PCP in HIV-positive patients with cancer requiring systemic antibiotics 1, 2

Approximately 60% of TMP-SMX-intolerant patients can tolerate dapsone 2

Clinical Pitfalls to Avoid

Do not assume normal G6PD status protects against hemolysis: Even patients with normal G6PD activity experience high rates of oxidant hemolysis in the stem cell transplant setting 3

Do not overlook heterozygous Cb5R deficiency: Heterozygosity for cytochrome b5 reductase deficiency may predispose to methemoglobinemia even on thrice-weekly dapsone regimens 5

Do not delay recognition in anemic patients: Cancer patients with underlying anemia become symptomatic at lower methemoglobin levels, potentially delaying detection 5, 4

Watch for hypersensitivity syndrome: "Sulfone syndrome" is a rare but serious reaction characterized by fever, exfoliative dermatitis, hepatic dysfunction, and methemoglobinemia occurring 1-4 weeks into therapy 2

Monitor for hepatotoxicity: Dapsone causes cholestatic injury and hepatic necrosis, leading to hemolysis and hepatitis due to iron overload in the liver 6