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LEUKEMIA: CHRONIC LYMPHOCYTIC
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Regimen/Number Of Patients |
Drug Dose and Route |
Leukopenia/ Neutropenia Toxicity |
Anemia Toxicity |
Other Grade III-IV Toxicities |
Emetogenic Potential |
Consequences of Adverse Event(s) |
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Alemtuzumab (Campath® prescribing information, Berlex Laboratories)
N = 149 |
Alemtuzumab 30 mg IV over 2 hours three times a week (initiate dosing at 3 mg IV daily; when tolerated [infusion-related toxicities are < Grade 2] increase to 10 mg). When the 10 mg dose is tolerated, the maintenance dose of alemtuzumab 30 mg can be initiated. Maintain at 30 mg TIW for up to 12 weeks. Appropriate premedications listed in Section 2, Commonly Used Premedication Regimens Note: Prophylaxis against PCP and herpes virus infections is strongly recommended, and should continue for 2 months after completion of alemtuzumab therapy, or until the CD4+ is > 200 calls/mL, whichever is later. |
Neutropenia Grade III-IV 64% |
Grade III-IV 38% |
Sepsis 10% Fever 19% Thrombocytopenia 50% Fatigue 5% Rigors 16% Hypotension 5% Bronchitis/ Pneumonia 13% Pneumonia 10% Urticaria 5% Dyspnea 9% |
Level 1 |
Gradual escalation to the recommended maintenance dose is required at the initiation of therapy and after interruption of therapy for 7 days or longer Hematologic toxicity is common―follow dose modification guidelines provded by the manufacturer
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2-CdA + P (Robak T, et al. Blood. 2000;96:2723-29)
N = 126
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Cladribine 0.12% mg/kg/d IV over 2 hours days 1-5 Prednisone 30 mg/m2/d PO days 1-5 Repeat cycle every 28 days for 3 courses |
Neutropenia Grade III-IV 9%
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Grade III-IV 2% |
FUO/infection* 56% Thrombocytopenia 9% Autoimmune Hemolytic Anemia* 6% Hepatic* 6% Nausea/Vomiting* 2% Diarrhea* 2% CNS 2% Eosinophilia* 9% Neuropathy* 2% Skin Reaction* 6%
*Grade unknown |
Days 1-5― level 1 |
Autoimmune hemolytic anemia-related deaths in 3% of patients Herpes zoster reactivation in 21% of patients; herpes simplex infections in 11% of patients URI or pneumonia in 30% of patients |
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C & P (Raphael B, et al. J Clin Oncol. 1991;9:770-76)
N = 60 |
Chlorambucil 30 mg/m2 PO day 1 Prednisone 80 mg/d PO days 1-5 Repeat cycle every 14 days |
Hematologic* 25%
*Severe/life threatening |
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Infection* 7% Fever** 2% Vomiting** 3%
*Severe/life-threatening ** Severe |
Day 1― level 1 |
Infectious mortality 2%
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LEUKEMIA: CHRONIC LYMPHOCYTIC (continued ) : Page 2
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Regimen/Number Of Patients |
Drug Dose and Route |
Leukopenia/ Neutropenia Toxicity |
Anemia Toxicity |
Other Grade III-IV Toxicities |
Emetogenic Potential |
Consequences of Adverse Event(s) |
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Chlorambucil (Dighiero G, et al. N Engl J Med. 1998;338:1506-14)
N = 301 |
Chlorambucil 0.1 mg/kg/d PO daily |
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Daily― level 1 |
66 second malignancies in chlorambucil arms over 72 months 48 second malignancies in observation arms over 67 months |
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Chlorambucil Prednisone (Dighiero G, et al. N Engl J Med. 1998;338:1506-14)
N = 460 |
Chlorambucil 0.3 mg/kg/d PO days 1-5 Prednisone 40 mg/m2 PO days 1-5 Repeat cycle every 28 days
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Days 1-5― level 1
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Cladribine (Robak T, et al. Leuk Lymphoma. 1996;22:509-14)
N = 110 |
Cladribine 0.12 mg/kg/d IV continuous infusion days 1-5 Repeat cycle every 28 days |
Grade III-IV 9.1% |
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Severe Infections* 12.7% Minor Infections and FUO* 33.7% Thrombocytopenia* 22.7%
*Grade unknown |
Days 1-5― level 1 |
Infections mortality 7.3% Hemorrhagic mortality 5.5%
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LEUKEMIA: CHRONIC LYMPHOCYTIC (continued ) : Page 3
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Regimen/Number Of Patients |
Drug Dose and Route |
Leukopenia/ Neutropenia Toxicity |
Anemia Toxicity |
Other Grade III-IV Toxicities |
Emetogenic Potential |
Consequences of Adverse Event(s) |
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Cyclophosphamide Fludarabine (O' Brien SM,et al,J Clin Oncol. 2001,9:1414-20) N=128 (dose-finding study;91 patients on the 300 mg/m2 dosing level) |
Cyclophosphamide 300 mg/m2/d IV over 1 hour days 1-3 Fludarabine 30 mg/m2/d IV over 30 minutes days 1-3 Repeat cycle every 4-6 weeks
Note: Prophylaxis with trimethoprim/sulfa- methoxazole recommended in patients receiving corticosteroids while undergoing treatment with this regimen for any reason. |
Neutropenia* Grade III 75% Grade IV 48%
*Toxicities reported are for the 300 mg/m2 dose level (n = 91) |
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Fever/ Infection * 40 % Thrombocytopenia * 19 % Fatigue / Aches * 2 % Nausea / Vomiting * 6% Rash * 2 %
* Toxicities reported are for the 300 mg/m2 dose level ( n= 91 ) |
Days 1-3 – Level 3 |
Documented sepsis or pneumonia was seen in 25% of patients during therapy Fever of unknown origin, often associated with neutropenia and requiring hospitalization , was observed in 25% of patients Six atypical infections were reported : 1 Pneumocystis carinii pneumonia, 1 cryptococcal bronchitis, 1 cryptococcal meningitis, 1 Vibrio sepsis, 1 strongyloides, 1 cytomegalovirus 5% of patients experienced herpes zoster infections 8% of patients developed reactivation of herpes simplex 29% of patients at the 300 mg/m 2 dose level required a dose reduction of cyclopphosphamide Prophylactic Ondansetron admininstered to all patients : howver, mild nausea requiring other oral agents occurred in 40% of patients. (nausea and vomiting typically occurred on day 3, and continued until day 4 or 5 ) 25% of patients were unable to complete 6 ourses of therapy as planned secondary to cumulative myelosuppression
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LEUKEMIA: CHRONIC LYMPHOCYTIC (continued ) : Page 4
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Regimen/Number Of Patients |
Drug Dose and Route |
Leukopenia/ Neutropenia Toxicity |
Anemia Toxicity |
Other Grade III-IV Toxicities |
Emetogenic Potential |
Consequences of Adverse Event(s) |
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Fludarabine (Keating MJ, et al. Blood. 1989;74:19-25)
N = 68 |
Fludarabine 25-30 mg/m2/d IV days 1-5* Repeat cycle every 28 days
*Phase I/II trial 2 dose levels |
Neutropenia Grade IV 56% (of cycles)
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FUO/Minor Infection 13% Pneumonia Septicamia 9% Thrombocytopenia* 25% Nausea* 3% Stomatitis* 2% Diarrhea* 2% Neuropathy* 4%
*Grade unknown |
Days 1-5― level 1 |
Infectious mortality 3% |
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Rituximab (Huhh D, et al. Blood. 2001;98:1326-31)
N = 30 |
Rituximab 375 mg/m2 IV every week for 4 weeks Appropriate premedications listed in section 2, Commonly Used Premedication Regimens |
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Grade III 3.4% |
Infection 17.1% Hypotension (Grade III) 3.4% Hypertension (Grade III) 6.8% Flu-like Symptoms (Grade III) 13.8% Abnormal Liver Function (Grade III) 6.8% Bone Pain (Grade III) 3.4% Pulmonary (Grade III) 6.8% Skin (Grade III) 3.4% (Grade IV) (zoster) 3.4% |
level 1 |
Due to a fatal treatment-related complication, the 375 mg/m2 dose on week 1 was fractionated patients received 50 mg on day 1, 150 mg on day 2, and the remainder of the dose on day 3 1 patients died of late pulmonary aspergillosis |