Introducing Patients to Fludara® (fludarabine phosphate) for injection

Using this patient education guide

FLUDARA^® (fludarabine phosphate) FOR INJECTION is an antineoplastic agent that is indicated for patients with refractory B-cell chronic lymphocytic leukemia (CLL) who have not responded to or whose disease has progressed during treatment with at least one standard alkylating agent–containing regimen.

Developed by other oncology nurses who counsel patients about therapy with FLUDARA^® FOR INJECTION, this guide has been designed to help you educate your patients who are about to begin treatment with this drug.

Introducing Fludara^® to your patients–
outlining the potential benefits

Studies conducted by the M.D. Anderson Cancer Center (MDACC)⁴ and the Southwest Oncology Group (SWOG)⁵ have shown that therapy with FLUDARA^® FOR INJECTION induces response in patients with refractory CLL.^* Retrospective analysis of the MDACC and SWOG studies according to stringent National Cancer Institute (NCI) criteria⁶ yielded overall objective response rates of 48% and 32%, respectively; in both studies, 13% of patients achieved complete response.⁷ Your patients should understand that although such response rates are impressive in heavily pretreated patients, not all patients respond to FLUDARA^® FOR INJECTION.

^* Please consult the full prescribing information for Fludara^®for complete information on efficacy and safety.

Encouraging patient education

When patients are well informed about their therapy, they become stronger partners in the fight against their disease. In addition to the continued education and support they receive from you, patients can obtain educational materials on CLL and other cancers by calling the local chapter of the Leukemia Society of America or its National Hotline for Information (800-955-4LSA), the local unit of the American Cancer Society or its national headquarters (800-ACS-2345), or the cancer information service of the NCI (800-422-6237).

Explaining the need for monitoring blood counts

FLUDARA^® FOR INJECTION is an antineoplastic agent and may cause significant myelosuppression. In clinical trials, the absolute neutrophil count decreased to less than 500/mm³ in 59% of 133 patients with CLL, hemoglobin decreased from pretreatment values by at least 2 g/dL in 60% of patients, and platelet count decreased from pretreatment values by at least 50% in 55% of patients. In a phase I study in solid tumor patients, the median time to nadir counts was 13 days (range, 3-25 days) for neutrophils and 16 days (range, 2-32 days) for platelets.⁷

Patients undergoing therapy should be observed for signs of hematologic and nonhematologic toxicity. They should be advised that periodic blood counts are necessary to detect anemia, neutropenia, and thrombocytopenia. If anemia develops, frequent rest periods and moderation of activities should be recommended to the patients. In addition, patients should understand that transfusions of packed red blood cells may be necessary. If thrombocytopenia occurs, patients should be advised to avoid aspirin and activities that could result in trauma. Some appropriate safety measures include use of an electric razor and soft toothbrush. Platelet transfusions may be required.

Instructing patients on signs of infection

Compromised immune function may occur in patients with certain hematologic malignancies. In the patient with CLL, for example, possible manifestations include autoimmune neutropenia, hypogammaglobulinemia, abnormal function and/or number of T cells or natural killer (NK) cells, and neutropenia secondary to bone marrow infiltration by the malignant clone of cells. In addition, therapy with FLUDARA^® FOR INJECTION may cause neutropenia, which results in increased susceptibility to infection.

Infection is a particular concern in the patient whose immune system has been compromised. Overall, 33% and 44% of patients in the MDACC and SWOG studies, respectively, developed infection.⁷ Infection was severe in 8% and 10% of patients, respectively. It is important, therefore, to instruct patients to report fever or local infection to you. You may want to ask them to monitor their temperature, especially if they feel warm or begin to have chills. Although patients should be instructed to avoid exposure to someone who is obviously ill, usually they will not have to avoid public places–shopping centers or movies, for example.

After the initial education process, most of the continuing questions that patients have are related to infection. They may range from what to do about a sore throat to questions about a fever.

Explaining bone marrow analysis

Physicians may elect to perform bone marrow analysis to confirm a clinical response to therapy. Because multiple courses of therapy may be required to achieve remission, bone marrow analysis is not usually performed until after a patient has received several courses of therapy, and some response has been observed.

Bone marrow analysis provides an accurate and sensitive way to assess response to therapy and duration of remission. According to NCI criteria,⁶ a complete response includes a bone marrow of normal cellularity, with lymphocytes less than 30% of nucleated cells; nodular collections of lymphocytes are permitted within the current definition of complete response.

Resolving patient anxiety about the adverse effects of therapy

Your patients may express anxiety that their "new" therapy is going to be considerably more toxic than their previous therapy (e.g., chlorambucil). In fact, FLUDARA^® FOR INJECTION is generally well tolerated. Although nausea and vomiting were reported in up to 36% of patients in the MDACC and SWOG studies, the incidence of severe nausea and vomiting was 2% or less⁷; therefore, medication with antiemetics prior to chemotherapy was not warranted in most patients. Similarly, the incidence of alopecia has been reported to be low (less than or equal to 3%). Thus, you can reassure your patients that severe nausea and vomiting and hair loss, often associated with many other chemotherapeutic regimens, are not encountered with FLUDARA^® FOR INJECTION in the vast majority of patients.

Explaining administration of Fludara^® For Injection

Patients who are beginning therapy with FLUDARA^® FOR INJECTION may need to be reassured that their new therapy need not disrupt their lives. Administration is usually performed on an outpatient basis in a hospital clinic or doctor's office; hospitalization is rarely required. Patients may be able to schedule the infusion before or after work or even during their lunch hour.

FLUDARA^® FOR INJECTION is administered intravenously over a period of approximately 30 minutes; the recommended dosage of FLUDARA^® FOR INJECTION is 25 mg/m² daily for 5 consecutive days; each 5-day course of treatment is repeated every 28 days. Acute infusion-related adverse events, such as anaphylaxis, orthostatic hypotension, rash, and syncope, are rare (less than 1%), and premedication with antiemetics is generally not necessary.

Decisions on venous access should be made after patient assessment. The drug is usually administered through a butterfly needle or short intravenous catheter; there is generally no need for long-term intravenous access. To date, there are no reports indicating that FLUDARA^® FOR INJECTION is a vesicant.

Discussing rare complications: tumor lysis syndrome, severe neurologic effects

Tumor lysis syndrome (TLS) is a rare but potentially serious complication of therapy. Patients at highest risk for TLS are those with bulky disease that responds rapidly to therapy. Monitoring blood count and chemistries (e.g., serum uric acid, phosphate, calcium, potassium, BUN, and creatinine), particularly during the first course of therapy, provides objective warning of TLS. In addition, you may want to recommend that patients at high risk of this syndrome increase their fluid intake (one 8-oz glass of water every hour) and report signs of TLS, such as flank pain and hematuria.

When dose-ranging clinical studies were performed to evaluate FLUDARA^® FOR INJECTION in patients with acute leukemia, severe neurologic effects, including coma, blindness, and death, were reported. This severe central nervous system toxicity occurred in 36% of patients treated with doses approximately four times greater (96 mg/m²/day for 5 to 7 days) than the recommended dose. In contrast, similar severe central nervous system toxicity has been reported rarely (less than or equal tob 0.2%) in patients treated at doses in the range of that recommended for CLL.^*

WARNING: FLUDARA FOR INJECTION should be administered under the supervision of a qualified physician experienced in the use of antineoplastic therapy. FLUDARA FOR INJECTION can severely suppress bone marrow function. When used at high doses in dose-ranging studies in patients with acute leukemia, FLUDARA FOR INJECTION was associated with severe neurologic effects, including blindness, coma, and death. This severe central nervous system toxicity occurred in 36% of patients treated with doses approximately four times greater (96 mg/m²/day for 5 to 7 days) than the recommended dose. Similar severe central nervous system toxicity has been rarely (less than or equal to 0.2%) reported in patients treated at doses in the range of the dose recommended for chronic lymphocytic leukemia.

Instances of life-threatening and sometimes fatal autoimmune hemolytic anemia have been reported to occur after one or more cycles of treatment with FLUDARA FOR INJECTION. Patients undergoing treatment with FLUDARA FOR INJECTION should be evaluated and closely monitored for hemolysis.

In a clinical investigation using FLUDARA FOR INJECTION in combination with pentostatin (deoxycoformycin) for the treatment of refractory chronic lymphocytic leukemia (CLL), there was an unacceptably high incidence of fatal pulmonary toxicity. Therefore, the use of FLUDARA FOR INJECTION in combination with pentostatin is not recommended.

^* Please consult the full prescribing information for Fludara^®for complete information on adverse neurologic effects.

References