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BREAST CANCER
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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) |
|
AC (Fisher B, et al, J Clin Oncol. 1997; 15:1858-69)
N= 764
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Doxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 Repeat cycle every 21 days
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Grade III 5% Grade IV 2% |
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Sepsis (Grade IV) 3% Neutropenic Infection 3 % Vomiting 14% Nausea (Grade III) 9% Diarrhea < 1% Stomatitis (Grade III) 1% Deep Vein Thrombosis 1% Cardiac < 1% |
Day 1 – Level 4 |
3% of patients withdrew due to toxicity
1 patient developed AML and 1 patient developed MDS after treatment
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ACT (Henderson IC, et al, Proc Am Soc Clin Oncol. 1998;17:101A, Abstract 390A)
N= 1,585
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Doxorubicin 60-90 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 Repeat cycle every 21 days x 4 cycles; then Paclitaxel 175 mg/m2 IV day 1 Repeat cycle every 21 days x 4 cycles Appropriate premedications listed in Section2, Commonly Used Premedicaiton Regimens
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Myelosuppression * (≥ Grade III) 21 % Neuropathy (≥ Grade III) 5% Pain (≥ Grade III) 5% Hyperglycemia (≥ Grade III) 5% Cardiac toxicityt 6%
Patients received G-CSF t Grade unknown
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See AC and Paclitaxel Regimens |
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CAF (FAC) (Stewart DJ, et al, J Clin Oncol 1997;15:1897-905 )
N= 128
|
Cyclophosphamide 500 mg/m2 IV day 1 Doxorubicin 50 mg/m2 IV day 1 5-Fluorouracil 500 mg/m2 IV day 1 Repeat cycle every 21 days |
Leukopenia Grade III 56% Grade IV 25% |
Grade III 7% Grade IV 2% |
Gastrointestinal 20% Stomatitis 2 % Alopecia 55 % Cardiac 1 % Thrombocytopenia 8 % |
Day 1 – Level 5 |
Delivered dose Intensity 93% 7% of patients had a Decrease in ejection fraction by ≥15% to a final level ≤ 45% |
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BREAST CANCER (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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Capecitabine (Blum JL, et al, J Clin Oncol. 1999;17:485-93 )
N= 162
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Capecitabine 1250 mg/m2 PO twice daily days 1-14 Repeat cycle every 21 days
Note: In reference, capecitabine administered as 1255 mg/m2 Po twice daily. |
Leukopenia 3% Neutropenia 3%
|
Grade III-IV4% |
Thrombocytopenia 4% Hand-Foot Syndrome*10% Diarrhea** 14 % Nausea * 4 % Vomiting * 4 % Fatigue * 7% Stomatitis * 3% Dehydration ** 4 % Hyperbilirubinemia **12% Elevated Alkaline Phosphatase 4 %
Severe, grade unknown ** Sever/life-threatening |
Days1-14 Level2 |
Discontinued therapy due to toxicity 4 % Life-threatening Diarrhea 3 % 1 patient developed an asymptomatic grade Iv coagulation disorder (elevated prothrombin time while receiving warfarin)
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Capecitabine Docetaxel (O'Shaughnessy, J, et al, J Clin Oncol 2002;20: 2812 – 23
N= 255
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Capecitabine 1250 mg/m2 PO twice daily Days 1- 14 Docetaxel 75 mg/m2 IV over 1 hour day 1 Repeat cycle every 21 days Appropriate premedications lised in Section 2, Commonly Used Premedication Regimens |
Neutropenia Grade III-IV 68 % |
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Neutropenic Fever 16 % Neutropenia ( Requiring medical Intervention) 16 % Stomatitis 17.4 % Diarrhea 14.4 % Nausea (Grade III ) 6 % Hand-Foot Syndrome ( Grade III) 24 % Alopecia (Grade III) 6% Fatigue/ Asthenia 8.4 % Hyperbilrubinemia 8.8 % ALT 1.6 % AST 2.8 %
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Day 1- Level 3 Days2-14- Level 2 |
Neutropenic fever Reqiring hospitalization 12% 45 patients (18%) Discontinued docetaxel, but continued capecitabine therapy. Capecitabine treatment was interrupted in 34 % of cycles, mainly for hand-foot syndrome (11.1%) diarrhea (8.5%), and stomatitis (4.6%) . Dose reductions for Adverse events occurred in 65 % of patients Capecitabine alone(4%) docetaxel alone(10%) or both agents (51%) The overall incidence of Grade III-IV adverse events was highest in the first treatment cycle (38%). In the second cycle, 36% of patients experienced Grade III-IV toxicities, Primarily Grade III Hand-foot syndrome. Death probably, possibly, or remotely related to edication in 3 patients . |
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BREAST CANCER (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) |
|
CMF ( Amodori D, et al, J Clin Oncol. 2000; 18: 3125-34
N = 138 |
Cyclophosphamide 100 mg /m2/d PO Days 1-1 4 Methotrexate 40 mg/m2 / IV days 1,8 5- Fluorouracil 600 mg/m2 IV days 1,8 Repeat cycle every 4 weeks |
|
|
Grade III |
Days 1,8- Level 3 |
Hematologic toxicity Required a delay of 1 week in 20.1 % of cycles and of 2 weeks in 4.3 % of cycles |
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CMF (Harper- Wynne C, et al. Br J Cancer. 1999; 81 : 316 – 22)
N = 48 |
Cyclophosphamide 600 mg /m2/IV days 1, 8 Methotrexate 40 mg/m2 / IV days 1,8 5- Fluorouracil 600 mg/m2 IV days 1,8 Repeat cycle every 28 days |
Leukopenia Grade III 14 % Grade IV 10 %
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Grade III 4 % |
Neutropenic Sepsis * 9 % Thrombocytopenia ( Grade IV) 4 % Alopecia ( Grade III) 8 % Nausea / Vomiting 19 % * Grade unknown |
Days 1, 8- Level 4 |
Dose reduction 21% due to hematologic toxicity 2 toxic deaths, one secondary to hematologic toxicity |
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Docetaxel ( Nabholtz JM, et al, J Clin Oncol. 1999; 17:1413-24)
N= 200 |
Docetaxel 100 mg/m2 IV over 1hr day1 Repeat cycle every 21 days Appropriate premedications listed in Section 2, Commonly Used Premedicaiton Regimens |
Grade III - IV 93% |
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Neutropenic Fever 9 % Infection ( ≥ Grade II fever with Grade IV neutropenia requiring hospitalization or antibiotics) 11 % Thrombocytopenia 4 % Nausea 5 % Vomiting 3 % Stomatitis 9 % Diarrhea 8 % Skin Toxicity 4 % Asthenia 16 % Neurosensory 5 % Sever fluid retention 8 % |
Day 1 – Level 2 |
Toxic mortality 2 % Treatment delay due to hematologic toxicity 6 % of patients Discontinued therapy due to toxicity 14 % Dose intensity 94 % |
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BREAST CANCER (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) |
|
Docetaxel Doxorubicin Cyclophosphamide ( Khayat D, et al, J Clin Oncol . 2001; 19: 3367-75)
N= 48 |
Docetaxel 100 mg/m2 IV day 1 Repeat cycle every 21 days for 4 cycles (Cycle 1- 4) Appropriate premedications listed in Section2, Commonly Used Premedication Regimens Followed by Doxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 Repeat cycle every 21 days for 4 cycles (Cycle 5 – 8 )
Consolidation According to Response to Initial Treatment Docetaxel 100 mg/m2 IV day 1 Repeat Cycle every 21 days for 3 cycles Appropriate premedications listed in Section2, Commonly Used Premedication Regimens OR Doxorubicin 60 mg/m2 IV day 1 Cyclophosphamide 600 mg/m2 IV day 1 Repeat Cycle every 21 days for 3 cycles
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Grade IV 68.8%
Grade IV 66.7%
Grade IV 62.1%
Grade IV 25% |
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Febrile Neutropenia (Grade IV neutropenia combined with Grade II fever ) 17 % Infection * 14 .6 %
Febrile Neutropenia (Grade IV neutropenia combined with Grade II fever ) 4.8 % Infection * 9.5 %
Febrile Neutropenia (Grade IV neutropenia combined with Grade II fever ) 7.1 %
Febrile Neutropenia (Grade IV neutropenia combined with Grade II fever ) 0%
Grade I or II, except for 1 patient with Grade III
Overall Nausea 4.2 % Stomatitis 8.3 % Vomiting 4.2 % Asthenia 10.4 % Nail Disorder 2.1 % Diarrhea 8.3 %
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Day 1 – level 2
Day 1- level 4
Day 1 – level 2
Day 1 – level 4 |
Duration of Grade IV neutropenia (median) 6 days Median relative Dose – intensity 98 %
Duration of Grade IV neutropenia (median) days Median relative Dose – intensity 89 %
Duration of Grade IV neutropenia (median) 7 days Median relative Dose – intensity 95 %
Duration of Grade IV neutropenia (median) 7 days Median relative Dose – intensity 83 %
Overall 1 patient withdrew Secondary to Asymptomatic LVEF Decrease after cycle 8 No deaths during study 6.4 % patients required IV antibiotics and /or hospitalization of 65 cycles that were delayed, 36 (55%) were due to hematologic side effects
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BREAST CANCER (continued ) : Page5
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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) |
|
Doxorubicin Docetaxel (Nabholtz JM, et al. 21st Annual San Antonio Breast Cancer Symposium, 1999. poster 330)
N= 213
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Doxorubicin 50 mg/m2 IV day 1 Docetaxel 75 mg/m2 IV day 1 Repeat cycle every 21 days Appropriate premedications listed in Section 2, Commonly Used Premedication Regimens |
Grade III-IV 97% |
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Febrile Neutropenia 33% Neutropenic infection (Grade III-IV) 8% Allergy 1% Nausea 6% Vomiting 6% Stomatitis 9% Diarrhea 8% Asthenia 9% Edema 1% Nail Changes 1% Cardiac * 6% Absolute decrease in ejection fraction = 20% |
Day 1- Level 4 |
Clinical CHF 3 % Median dose Intensity 96% Discontinue due To toxicity 14%
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Doxorubicin Docetaxel (Sparano JA, et al, J Clin Oncol. 2000;18:2369-77)
N= 51
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Doxorubicin 60 mg/m2 IV day 1 Followed 1 hour later by Docetaxel 60 mg/m2 IV over 1 hour day 1 G-CSF 5 mcg/kg/d SQ starting day 2 Until ANC ≥ 10,000 Repeat cycle every 21 days Appropriate premedications listed in Section 2, Commonly Used Premedication Regimens
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Granulocytopenia Grade III 7% Grade IV 69%
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Grade III 7% Grade IV 2% |
Febrile Neutropenia (Grade III)2% Infection (Grade III-IV) 17% Thrombocytopenia 16% Nausea 13% Vomiting 10% Stomatitis 6% Neuromotor (Grade III) 4% Cardiac 6% Diarrhea 8% Fatigue (Grade III) 2% Hypertention (grade III) 2% Edema (Grade III) 2% Hypersensitivity Reaction (Grade III) 2% |
Day 1 – Level 4 |
2 septic deaths (in patients with hepatic impairment ) |
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Doxorubicin Paclitaxel (Jassem J, et al. J Clin Oncol 2001; 19: 1707-15)
N= 128 | ||||||