What is cytoreductive therapy?

What is Cytoreductive Therapy?

Cytoreductive therapy is medical treatment aimed at reducing the number of abnormal blood cells or tumor burden in the body, primarily using medications like hydroxyurea, interferon, or other agents to control excessive cell production and prevent complications. 1

Definition and Purpose

Cytoreductive therapy refers to treatment strategies that reduce pathologic cell populations through pharmacologic means. 2 The primary goals include:

• Reducing thrombotic risk by controlling elevated blood cell counts (platelets, white blood cells, red blood cells) 1
• Preventing disease-related complications such as bleeding, splenomegaly, and progression to more severe disease states 1
• Controlling disease-related symptoms including pruritus, night sweats, fatigue, and progressive splenomegaly 1

Context in Hematologic Diseases

In myeloproliferative neoplasms (polycythemia vera and essential thrombocythemia), cytoreductive therapy specifically targets the excessive production of blood cells that characterizes these disorders. 1, 3 The therapy works by suppressing the overactive bone marrow to normalize blood counts and reduce the risk of life-threatening thrombotic events. 1, 3

Specific Indications for Initiation

Cytoreductive therapy should be initiated when patients develop: 1

• New thrombosis or disease-related major bleeding
• Frequent or persistent need for phlebotomy (≥3 per year in polycythemia vera)
• Symptomatic or progressive splenomegaly
• Symptomatic thrombocytosis
• Progressive leukocytosis (WBC >10 × 10⁹/L)
• Progressive disease-related symptoms (pruritus, night sweats, fatigue)

Context in Solid Tumors

In ovarian cancer and other solid malignancies, cytoreductive therapy takes a different form—cytoreductive surgery—which involves the physical removal of tumor tissue to reduce overall tumor burden. 1 The goal is resection of all visible disease or reduction to residual tumor nodules less than 1 cm in maximum diameter. 1 This surgical approach aims to improve the effectiveness of subsequent chemotherapy by minimizing the volume of disease that must be treated systemically. 1

Common Cytoreductive Agents

First-Line Options

Hydroxyurea is the most commonly used cytoreductive agent, with Level II, A evidence supporting its use as first-line therapy. 1, 3 Standard dosing is 2 g/day (2.5 g/day if body weight >80 kg) for at least 3 months to assess response. 4, 5

Interferon alfa (including peginterferon alfa-2a and alfa-2b) represents an alternative first-line option, particularly preferred for: 1, 3

• Younger patients (<40 years)
• Pregnant patients requiring cytoreductive therapy
• Patients with refractory pruritus
• Patients who defer hydroxyurea due to leukemogenic concerns

Second-Line Options

Ruxolitinib is FDA-approved specifically for polycythemia vera patients who have had inadequate response to or are intolerant of hydroxyurea. 1 This represents the primary second-line option when hydroxyurea fails. 1, 3

Anagrelide can be considered for essential thrombocythemia. 1, 2

Agents to Avoid

Busulfan should not be used except possibly in elderly patients >70 years, as it carries significant risk of transformation to acute myeloid leukemia and increased risk of second malignancies, especially when used sequentially with hydroxyurea. 1, 3

Monitoring and Response Assessment

Response to cytoreductive therapy should be monitored every 3-6 months or more frequently if clinically indicated. 1, 5 Key monitoring parameters include:

• Hematocrit levels (target <45% in polycythemia vera)
• Complete blood count with attention to platelet count (target <400 × 10⁹/L) and WBC count (target <10 × 10⁹/L)
• Assessment for new thrombosis or bleeding events
• Evaluation of disease-related symptoms using standardized tools like MPN-SAF TSS
• Bone marrow aspirate and biopsy as clinically indicated to rule out disease progression

1, 3, 5

Critical Distinction from Other Therapies

Cytoreductive therapy differs fundamentally from curative-intent treatment. 6 While it aims to control disease burden and prevent complications, it does not typically eradicate the underlying disease process in chronic myeloproliferative disorders. 1, 2 The therapy is generally continued long-term as maintenance treatment rather than administered for a defined curative course. 1, 7

In contrast to palliative surgery, cytoreductive surgery in solid tumors is performed with the specific intent of enhancing subsequent systemic therapy effectiveness, not merely for symptom relief. 1