BREAST CANCER

 

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

 

Doxorubicin 60 mg/m2 IV day 1

Cyclophosphamide 600 mg/m2 IV day 1

Repeat cycle every 21 days

 

Grade III 5%

Grade IV 2%

 

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

 

ACT

(Henderson IC, et al,

Proc Am Soc

Clin Oncol.

1998;17:101A,

Abstract 390A)

 

 

N= 1,585

 

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

 

 

 

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

 

 

 

See AC and

Paclitaxel

Regimens

 

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%

 

 

 

 

 

BREAST CANCER  (continued ) : page 2

 

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)

Capecitabine

(Blum JL, et al,

J Clin Oncol.

1999;17:485-93 )

 

 

N= 162

 

 

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)

 

 

 

 

 

Capecitabine

Docetaxel

(O'Shaughnessy, J, et al,

J Clin Oncol

2002;20: 2812 23

 

 

N= 255

 

 

 

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 %

 

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 %

 

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 .

 

 

 

BREAST CANCER  (continued ) : page 3

 

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

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 %

 

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

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%

 

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 %

 

 



 

 

 

BREAST CANCER (continued ) : page 4

 

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

 

 

 

Grade IV 68.8%

 

 

 

 

 

Grade IV 66.7%

 

 

 

 

 

 

Grade IV 62.1%

 

 

 

 

Grade IV 25%

 

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 %

 

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

 

 

 

  

 

 

 

 

BREAST CANCER  (continued ) : Page5

 

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

 

 

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%

 

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%

 

Doxorubicin

Docetaxel

(Sparano JA, et al,

J Clin Oncol.

2000;18:2369-77)

 

N= 51

 

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

 

 

Granulocytopenia

Grade III 7%

Grade IV 69%

 

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 )

Doxorubicin

Paclitaxel

(Jassem J, et al.

J Clin Oncol

2001; 19: 1707-15)

 

 

N= 128

 

 

Doxorubicin 50 mg/m2 IV day 1,

followed 24 hours later by

Paclitaxel 220 mg/m2 IV over 3 hours day 2

Repeat cycle every 21 days

Appropriate premedications listed in Section 2,

Commonly Used Premedication Regimens

Neutropenia

Grade III 27 %

Grade IV 62 %

Grade III-IV 9%

Infection (Grade III ) Fever 8 %

Thrombocytopenia (Grade IV )2 %

Arthralgia/Myalgia (Grade III ) 10%

Pripheral Neuropat, (Grade III ) 12%

Nausea/ Vomiting (Grade III ) 8%

Diarrhea 3 %

Stomatitis (Grade III ) 1%

Day 1

Level 3

Day 2

Level 2

Significant decrease

In LVEF in 21 %

Of patients

 

 

 

 

 

BREAST CANCER (continued ) : Page 6

 

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)

FEC 100

(French Adjuvant Study

Group. J Clin Oncol.

2001;19:602-11)

 

 

N= 276

 

5-Fluorouracil 500 mg/m2 IV day 1

Epirubicin 100 mg/m2 IV day 1

Cyclophosphamide 500 mg/m2 IV day 1

Repeat cycle every 21 days

 

Neutropenia

Grade III-IV

25.2 %

Grade III 0.8

Infection (Grade III ) 3.4 %

Nausea / Vomiting 34.7 %

Stomatitis 3.8 %

Alopecia 78.8 %

 

Day 1

Level 5

4 cases of delayed

cardiac toxicity

 

Gem-Cis

(Nagourney RA, et al,

J. Clin Oncol.

2000; 18: 2245-49 )

 

 

N= 30

Cisplatin 30 mg/m2 IV days 1,8, followed by
Gemcitabine 750 mg/m2 IV days 1,8

Repeat cycle every 21 days

Leukopenia

Grade III-IV

%

Neutropenia

Grade III-IV

10 %

Grade III-IV 4 %

Nausea/ vomiting

(Grade III) 4 %

Thrombocytopenia 31 %

Day 1 -

Level 5

 

NFL

(Hainsworth JD,

Dur J Cancer Care.

1997; 6: 4 -9 )

 

 

N= 64

Mitoxantrone 12 mg/m2 IV day 1

5- Fluorouracil 350 mg/m2 /d IV bolus

days 1-3, given after leucovorin Leucovorin 300 mg/m2 /d IV over 30-60 minutes days 1-3

Leukopenia

Grade III-IV

4 %

 

 

 

 

Neutropenic Fever 4 %

Thrombocytopenia 1 %

Nausea/ Vomiting < 1 %

Mucositis 2 %

Diarrhea 3 %

Conjunctivitis 1 %

Alopecia 8 %

 

Day 1

Level 4

Days 2, 3

Level 2

4 % hospitalized

43% of cycles had  a dose reduction

due to toxicity

 

Paclitaxel

(Smith RE, et al .

J Clin  Oncol.

1999; 17: 3403-11

 

 

N= 279

 

 

N= 284

Paclitaxel 250 mg/m2 IV over 3 hrs day 1

Repeat cycle every 21 days

OR

 

Paclitaxel 250 mg/m2 IV over 24 hrs day 1

Repeat cycle every 21 days

Appropriate premedications listed in Section 2,

Commonly Used Premediction Regimens

Neutropenia

Grade III-IV

73 %

 

 

Grade III-IV

81 %

 

 

 

 

3 hr 24 hr

Febrile Neutropenia

5 %      18 %

Infection      7%       12 %

Alopecia        59%     68%

Nausea           4 %      8 %

Vomiting        3%       8%

Diarhea          1%       4 %

Neurosensory  22 %   13%

Neuromotor     17%    12%

Arthralgia / Myalgia

19%     19%

Hypersensitivity

2 %      1%

 

Day 1-

Level 2

Toxic deaths 3% (3hr),

1% (24 hr)

Discontinuation due to

toxicity 20% (3hr)

and 15 % (24 hr)

Toxicity ≥ Grade IV

Was more common

In the 24 hours group

(23% vs 12 % )

Paclitaxel Weekly

(Perez EA, et al.

J Clin Oncol.

2001; 19:4216-23)

 

 

N= 212

Paclitaxel 80 mg/m2  over 1 hour weekly

for  4 weeks

Repeat cycle every 28 days

Appropriate premedications listed in Section2,

Commonly Used Premedication Regimens

Neutropenia

Grade III 10%

Grade IV 5%

Grade III 9 5

Arthralgia / Myalgia 2 %

Neuropathy (Grade III) 9 %

Asthenia 4 %

 

 

Level 2

 

 

 

 

BREAST CANCER  (continued ) : Page 7

 

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)

Paclitaxel

Epirubicin

(Rischin D, et al,

Br J Cancer.

2000; 83:483-42 )

 

 

N= 43

Epirubicin 75 mg/m2 IV day 1, followed by

Paclitaxel 175 mg/m2 IV over 3 hours day 1

Repeat cycle every 21 days

Appropriate premedications listed is Section 2,

Commonly Used Premedication Regimens

Neutropenia

Grade III 2%

Grade IV 95%

Grade III 7%

Infection (Grade III) 19%

Febrile Neutropenia 14%

(4% of cycles)

Thrombocytopenia 7%

Stomatitis (Grade III) 5%

Nausea (Grade III) 7%

Vomiting (Grade III) 2 %

Diarrhea 4 %

Myalgia/Arthralgia

(Grade III) 14 %

Asthenia (Grade III) 12 %

 

Day 1

Level 4

9.3%  of patients required

dose delays due to

slow recovery from

myelosuppression

42% of patients required

dose reductions

predominantly for

low blood counts and

febrile neutropenia

Paclitaxel-Vinorelbine

(Romero Acuna L. et al,

J Clin Oncol.

1999; 17: 74-81)

 

 

N= 49

Vinorelbine 30 mg/m2 IV days 1, 8

Paclitaxel 135 mg/m2 IV over 3 hrs, days 1*

Repeat cycle every 28 days

Appropriate premedications listed in Section 2,

Commonly Used Premedication Regimens

 

 

*Administer 1 hour after vinorelbine infusion

on day 1 of each cycle

Leukopenia

Grade III 61%

Grade IV 32%

Neutropenia

Grade III 22%

Grade IV 71%

 

Grade III 12 %

Infection (most

common with

increased LFTs) 18%

Thrombocytopenia

(grade IV) 4%

Constipation (Grade III) 2%

Nausea / Vomiting

(Grade III) 2%

Alopecia (Grade III) 86%

Phlebitis (Grade III) 12 %

 

Day 1

Level 2

Day 8

Level 1

Dose reductions occurred

in 98% of patients due

to hematologic toxicity

At cycle 6 the delivered

dose intensity was

62% and 65%  of that

planned for vinorelbine

and paclitaxel,

respectively

Septic death 4%

Trastuzumab

Docetaxel

(Esteva FJ, et al,

J Clin Oncol.

2002; 20:1800-8)

 

 

N= 30

 

Cycle  1

Trastuzumab 4 mg/kg IV loading dose over

90 minutes on day 0 of cycle 1, followed

by 2 mg/kg iv weekly on days 8, 15

Docetaxel 35 mg/m2 IV days 1,8 15*

Appropriate premedications listed in Section 2

Commonly Used Premedication Regmens

 

Subsequent cycles

Trastuzumab 2 mg.kg IV weekly

On days 1, 8, 15, followed by

Docetaxel 35 mg/m2 IV days 1, 8, 15

Repeat cycle every 28 days

Appropriate premedications listed in Section 2,

Commonly Used Premedication Regimens

 

 

*On first week of treatment, the dose of

Trastuzumab precedes docetaxel, On all subsequent cycles, the dose of docetaxel  precedes trastuzumab

 

Granulocytopenia

Grade III 16%

Grade IV 10%

 

Grade I-II 56%

 

Neutropenic Fever

(Grade III) 3%

Fatigue (Grade III) 20%

Thrombocytopenia 0 %

Neuropathy (Grade III) 3 %

Left Ventricular Dysfunction

(Grade III) 3%

Pleural Effusion

(Grade III) 3 %

Diarrhea (Grade III) 6 %

Hypersensitivity Reaction

(Grade III) 6 %

Days 1, 8, 15-

Level 2

Docetaxel was

discontinued

because of  toxicity

in 23 % of patients

Excessive lacrimation

(Grade I-II) developed

in 93% of patients at

a median cumulative

dose of 210 mg/m2

docetaxel

Grade I-II edema

occurred in 46% of

patients, and occurred

at a median docetaxel

dose of 220 mg/m2

Median dose intensity

of docetaxel was 91%

63% of patients required

a dose reduction

of docetaxel