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LYMPHOMA :NON HODGKIN'S LYMPHOMA
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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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Bexarotene (Duvic M, et al. J Clin Oncol . 2001;19:2456-71)
N= 56
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Bexarotene 300 mg/m2/d Po daily |
Leukopenia Moderate 7.1% Moderately Severe 3.6% Severe 2.6% |
Moderately Severe 1.8% |
Moderately Severe = MS Severe = S Infection (S) 1.8% Asthenia (MS) 1.8% Headache (MS) 3.6% Pain (MS) 3.6 % Edema 5.4% Diarrhea (MS) 1.8% Hypothroidism 3.6% Increased Cholesterol (MS) 1.8% Hyperlipidemia 33.9% Exfoliation (S) 1.8% Pruritis 14.2% Rash (S) 3.6% Skin Disorder 10.7% |
Nausea― level 1 |
Dose limiting toxicities occurred in 66% of patients (50% at 300 mg/m2/d and 89% at 300 mg/m2/d) Monitor for hyperlipidemia |
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CHOP (Bjorkholm M, et al. Blood. 1999;94:599 a)
N= 104 |
Cyclophosphamide 750 mg/m2 IV day 1 Doxorubicin 50 mg/m2 IV day 1 Vincristine 1.4 mg/m2 IV day 1 (maximum 2 mg) Prednisone 100 mg/d Po days 1-5 Repeat cycle every 21 days |
Grade IV 91 % (Note: combined data w/ CNOP) |
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Day 1― level 4 |
Hospitalization due to neutropenic fever 47% Delivered dose intensity of doxorubicin 92% and cyclophosphamide 94% |
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CHOP plus Rituximab (Coiffier B, et al. N Engl J Med . 2002;346:235-42)
N= 202
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Rituximab 375 mg/m2 IV day 1 Cyclophosphamide 750 mg/m2 IV day 1 Doxorubicin 50 mg/m2 IV day 1 Vincristine 1.4 mg/m2 (maximum 2 mg) IV day 1 Prednisone 40 mg/m2/d Po days 1-5 Repeat cycle every 21 days
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After cycle 1 Median ANC Nadir 400/mm3 |
Grade III-IV 14% |
Fever 2% Infection 12% Herpes Zoster 4% Infusion-Related 9% Mucositis 3% Liver Toxicity 3% Cardiac Toxicity 8% Neurologic Toxicity 5% Renal Toxicity 1% Lung Toxicity 8% Nausea/Vomiting 4% Constipation 2% Alopecia 39% Other Toxicities 20% |
Day 1― level 4 |
deaths not attributed to primary disease 37% required G-CSF by cycle 4, 43% by cycle 8 |
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CNOP (Paviovsky S, et al. Ann Oncol. 1992;3:205-09)
N = 45 |
Cyclophosphamide 750 mg/m2 IV day 1 Mitoxantrone 10 mg/m2 IV day 1 Vincristine 1.4% mg/m2 IV day 1 Prednisone 50 mg/m2/d PO days 1-5 Repeat cycle every 21 days |
Mean Nadir ANC 600/mm3 Mean Nadir WBC × 109 (0.3 to 5.0)
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Stomatitis 2% Nausea/Vomiting 16% Alopecia 24% Cardiac 2% Neurologic 7% Diarrhea 2% Cutaneous 2% |
Day 1― level 4 |
Infectious mortality 11% Hospitalization for neutropenic fever 48% |
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LYMPHOMA: NON-HODGKIN’S (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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CODOX-M-IVAC CODOX-M (Magrath I, et al. J Clin Oncol. 1996;14:925-34)
N = 41 |
Cyclophosphamide 800 mg/m2 IV day 1, then 200 mg/m2/d IV days 2-5 Vincristine 1.5 mg/m2 IV days 1, 8 in cycle 1 and on days 1, 8, and 15 on cycle 3 Doxorubicin 40 mg/m2 IV day 1 Cytarabine intrathecal 70 mg days 1, 3 Methotrexate 1200 mg/m2 IV over 1 hour, followed by 240 mg/m2/hour for the next hours starting on day 10 Calcium leucovorin 192 mg/m2 IV to start hours after the completion of the methotrexate infusion × 1 dose, then mg/m2 IV every 6 hours until the methrotrexate level is < 5×10-8 mol/L GM-CSF 7.5 mcg/kg/d subcutaneously day 13 onwards until ANC > 1000 Methotrexate 12 mg intrathecal (IT) day 15
Notes: patients with CNS disease at presentation received additional intrathecal therapy during the first CODOX-M cycle with IT cytarabine day 5 and IT MTX day 17. Regimen consists of alternating cycles of CODOX-M and IVAC for a total of 4 cycles |
Neutropenia Grade IV 97.6% cycles (< 18 years) Grade IV 97.8% (≥ 18 years) Leukopenia Grade IV 97.6% cycles (< 18 years) Grade IV 95.6% cycles (≥ 18 years) |
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Thrombocytopenia (Grade III) 17.1% (< 18 years) and 9.3% (≥ 18 years) Thrombocytopenia (Grade IV) 53.7% (< 18 years) and 39.5% (≥ 18 years) Stomatitis (Grade III) 26.8% (< 18 years) and 28.9% (≥ 18 years) Stomatitis (Grade IV) 41.5% (< 18 years) and 20% (≥ 18 years) Hepatotoxicity (Grade III) 24.4% (all ages) Hepatotoxicity (Grade IV) 2.4% (all ages) |
Day 1― level 5 Days 2-5― level 2 Day 8― level 1 Day 10― level 4 |
Infections documented in 46.6% of cycles Sepsis occurred in 22.1% of cycles overall Average duration of neutropenia was days (range 0-22) Systemic fungal infections in patients: 1 pulmonary aspergillosis 1 Candida tropicalis 11 patients developed a profound and painful disabling neuropathy (thought to be due to the concomitant administration of growth factors and vincristine) |
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LYMPHOMA: NON-HODGKIN’S (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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IVAC (Magrath I, et al. J Clin Oncol. 1996;14:925-34)
N = 41 |
Etoposide 60 mg/m2/d IV over 1 hour days 1-5 Ifosfamide 1500 mg/m2/d IV over 1 hour days 1-5 Mesna 360 mg/m2/d IV over 1 hour (1 dose mixed with ifosfamide), followed by mesna 360 mg/m2/d IV over 15 minutes every 3 hours days 1-5 Cytarabine 2000 mg/m2/d IV over 3 hours every 12 hours on days 1, 2 (a total of 4 doses) Methotrexate intrathecal 12 mg × 1 on day 5 GM-CSF 7.5 mcg/kg/d SQ day 7 onwards
Notes: Regimen consists of alternating cycles of CODOX-M and IVAC for a total of 4 cycles. patients with CNS disease at presentation receive additional IT therapy during the 1st cycle of IVAC as follows: IT cytarabine on days 7 and 9. |
Neutropenia Grade IV 100% (all ages) Leukopenia Grade IV 100% (all ages) |
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Thrombocytopenia (Grade III): 14.3% cycles (< 18 years) 3.7% (≥ 18 years) Thrombocytopenia (Grade IV) 82.9% cycles (< 18 years) 96.3% (≥ 18 years) Hepatotoxicity (Grade III) 5.9% cycles (< 18 years) Stomatitis (Grade III) 5.7% cycles (< 18 years) 3.4% cycles (≥ 18 years) Stomatitis (Grade IV) 2.9% cycles (< 18 years)
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Day 1-2― level 5 Day 3-5― level 4 |
Documented infections in 54.5% of cycles (all patients) Average duration of neutropenia 11 days (range 5-33) |
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Denileukin diftitox (Olsen E, et al. J Clin Oncol. 2001;19:376-88)
N = 71 |
Denileukin diftitox 9 or 18 mcg/kg/d IV days 1-5 Repeat cycle every 21 days Premedicate with acetaminophen and antihistamines Premedication with corticosteroids not permitted |
9 mcg/kg Leukopenia 6% Neutropenia 3%
18 mcg/kg Leukopenia 3% Neutropenia 3% |
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Infection 33%-43% Infusion-Repeat Events Back pain 6%-11% Chest pain/ Tightness 9% Pruritis 6% Hypotension 8%-11% Vasodilation 3% Dyspnea 6%-11% Constitutional Symptoms 37%-47% Gastrointestinal 20%-36% Vascular Leak Syndrome 17%-25% Thrombotic Events 3%-8% Rash 19%-23% Right Heart Failure 3%-6% CNS 17%-25% |
Days 1-5― level 2 |
31% of patients withdrew due to toxicity Vascular leak syndrome is more pronounced in patients with albumin < 3 g/dl |
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LYMPHOMA: NON-HODGKIN’S (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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DHAP (Valasquez WS, et al. Blood. 1988;71:117-22)
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Dexamethasone 40 mg/d PO or IV days 1-4 Cisplatin 100 mg/m2/d IV continuous infusion day 1 Cytarabine 2000 mg/m2 IV every 12 hours for 2 doses, day 2 Repeat cycle every 21 to 28 days
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Neutropenia Grade IV 53% |
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Neutropenic Infection 31% Thrombocytopenia* 39% Renal** 20% Gastrointestinal† 20% Neurological†† 6% Respiratory†† 6% Tumor Lysis Syndrome†† 5%
*Grade IV toxicity **SCr > double baseline value †Severe ††Grade unknown |
Day 1― level 5 Day 2― level 4 |
Infectious mortality 11% Hospitalization for neutropenic fever 48% Mortality secondary to tumor lysis syndrome 3% |
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ESHAP (Valasquez WS, et al. J Clin Oncol. 1994;12:1169-76)
N = 122 |
Etoposide 40 mg/m2/d days 1-4 Methylprednisolone 250-500 mg/d IV days 1-5 Cisplatin 25 mg/m2/d IV continuous infusion days 1-4 (total 100 mg/m2) Cytarabine 2000 mg/m2 IV day 5 Give immediately following completion of etoposide and cisplatin Repeat cycle every 21-28 days |
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Febrile Neutropenia 30% Nausea/Vomiting (Grade III) 6% Renal (SCr > double baseline) 22%
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Days 1-4― level 5 Day 5― level 4 |
Infectious mortality 4% Hospitalization (admitted for antibiotics) 30% Premanent renal toxicity 4% |
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Etoposide Carboplatin Ifosfamide (Moskowitz CH, et al. J Clin Oncol. 1999;17:3776-85)
N = 163 |
Etoposide 100 mg/m2/d IV days 1-3 Carboplatin AUC of 5 (maximum dose 800 mg) IV day 2 Ifosfamide 5 g/m2 IV continuous infusion over 24 hours day 2 (with 100% replace- ment with mesna) G-CSF 5 mcg/kg/d SQ days 5-12 |
Neutropenia 20.8% |
Grade III-IV 26.5% |
Thrombocytopenia 29.4% Neurotoxicity (not graded) 3% Increased Alkaline Phosphatase (2x) 11% Increased Alanine Transferase (2x) 9.8% |
Day 1― level 2 Day 2― level 5 Day 3― level 2 |
12.9% of Grade IV neutropenia patients hospitalized |
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LYMPHOMA: NON-HODGKIN’S (continued ) : Page 5
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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 Cyclophosphamide (Flinn IW, et al. Blood. 2000;96:71-75)
N = 60 |
Fludarabine 20 mg/m2/d IV days 1-5 Cyclophosphamide 600 mg/m2/d IV day1 G-CSF 5 mcg/kg SQ starting day 8 continuing 10-14 days until ANC ≥ 10,000 Trimethoprim/sulfamethoxazole PO twice daily every Mondey, Wednesday, Friday Allopurinol 300 mg daily day 1-7 cycle 1 only Repeat cycle every 28 days |
Neutropenia Grade III 20% Grade IV 8% |
Grade III-IV 7% |
Thrombocytopenia (Grade III) 1.6% Pulmonary (Grade III) 3.3% |
Day 1― level 3 Days 2-5― level 1 |
Viral reactivation in 6.7% of patients
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Fludarabine Cyclophosphamide (Hochster HS, et al. J Clin Oncol. 2000;18:987-94)
N = 27 (16 in the recommended dosing cohort) |
Cyclophosphamide 1000 mg/m2 IV day 1 Fludarabine 20 mg/m2/d IV over 30 minutes days 1-5 Repeat cycle every 28 days
Note: PCP and antiviral prophylaxis were routinely administered. |
Neutropenia (all cycles) Grade III 25% of cycles Grade IV 18% of cycles Neutropenia (cycle 1, without growth factor) Grade III 26% Grade IV 28% |
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Infectious toxicity 11% Pulmonary toxicity 18%
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Day 1― level 4 Days 2-5― level 1 |
Herpes Zoster radiculo- pathy in 3 patients Treatment discontinued secondary to toxicity in 6 patients: prolonged cytopenias pulmonary toxicities Pneumocystis carinii pneumonia in 1 patient
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Fludarabine Mitoxantrone (Dimpoulos MA, et al. Leuk Lymphoma. 2002;43:111-14)
N = 27 |
Fludarabine 25 mg/m2/d IV over 30 minutes days 1-3 Mitoxantrone 10 mg/m2 IV day 1 Repeat cycle every 28 days |
Neutropenia Grade III 22% Grade IV 18%
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Neutropenic Fever 11% Alopecia 11%
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