LUNG CANCER: SMALL-CELL

 

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)

CAV (VAC)

(Fukuoka M, et al,

J Natl Cancer Inst.

1991;83:855-61)

 

N= 97

 

Cyclophosphamide 800 mg/m2 IV-day 1

Doxorubicin 50 mg/m2 IV day 1

Vincristine 1.4 mg/m2 (maximum 2 mg) IV

day  1

Repeat cycle every 21-28 days

Leukopenia

Grade III 42%

Grade IV 36 %

 

 

Nausea/Vomiting

(Grade II-IV ) 64%

Thrombocytopenia 13%

Neuropathy

(Grade II-IV) 9%

Hepatic (Grade II-IV) 11%

Renal (Grade II-IV) 4%

Alopecia (Grade II-IV) 72%

Day 1 –

Level 5

Toxic mortality 3 %

 

EC

( Kosmidis PA, et al,

Semin Oncol,

1994;21:23-30)

 

N= 72

Etoposide 100 mg/m2/d IV  days 1-3

Carboplatin 300 mg/m2  IV days 1

Repeat cycle every 21 days

Leukopenia

Grade III 10 %

Grade IV 7 %

 

 

Neutropenic Infection

(all grades ) 11 %

Thrombocytopenia

(Grade IV)  4 %

Alopecia (Grade III) 7 %

 

 

Day 1 –

Level 5

Days 2, 3-

Level

Delivered dose intensity

80 % for carbo and

81 % for etoposide

Treatment delay 3 %

EP

( Pujol JL, et  al.

J Natl Cancer Inst.

2001;93:300-08)

 

N= 109

 

Etoposide 100 mg/m2/d IV days 1 – 3

Cisplatin 100 mg/m2  IV day 2

Repeat cycle every 28 days

Neutropenia

Grade III-IV

85%

 

Grade III-IV 18%

Documented Infections

(all grades ) 8 %

Fever (all grades) 18 %

Nausea/Vomiting 19 %

Thrombocytopenia  18 %

Creatinine Increase 12 %

Bilirubin Increase 2 %

 

Days 1, 3 –

Level 2

Day 2 –

Level

RBC transfusions 13 %

Platelet transfusions 5 %

Antibiotic infusions 26%

Toxic death 5.5 %

Early termination

of therapy due

to toxicity 5%

Irinotecan-Cisplatin

(Noda K, et  al,

N Engl J Med.

2002;346:85-91)

 

N= 75

Irinotecan 60 mg/m2 days 1, 8, 15

Cisplatin 60 mg/m2 on day 1 only

Repeat cycle every 28 days X  4 cycles

JCOG Criteria :

Neutropenia

Grade III 40 %

Grade IV 25.3 %

 

Grade III 26.7%

Fever (Grade III 1.3%

Infection 5.3 %

Thrombocytopenia 5.3 %

Diarrhea 16 %

Nausea/Vomiting

(Grade III) 13.3%

Decreased Arterial

Oxygen Pressure 5 %

Abnormal Liver Enzymes

(Grade III ) 4 %

Day 1 –

Level 5

Days 8,

15-

level  II

There were 3 treatmet

related deaths

(bleeding,

neutropenia/diarrhea,

and pneumonia )

PCDE

(Pujol JL, et al,

J Natl Cancer Inst.

2001;93:300-08)

 

 

N= 117

 

Etoposide 100  mg/m2/d IV days 1 -3

Cisplatin 100 mg/m2/d IV day 2

Cyclophosphamide 400 mg/m2/d IV days 1 -3

Epirubicin 40 mg/m2 IV day 1

Repeat cycle every 28 days

Neutropenia

Grade III- IV

99%

 

 

 

Grade III-IV 51 %

Documented Infections

(all grades ) 22 %

Fever (all grades ) 70 %

Nausea / Vomiting 22 %

Thrombocytopenia 78 %

Creatinine Increase 6 %

Bilirubin Increase 1 %

Days 1 – 2-

Level 5

Day 3 –

Level 4

RBC transfusions 45%

Platelet transfusions 38%

Antibiotic infusions 67 %

Cardiac toxic death 8 %

Early termination

of therapy due

to toxicity 15 %

 

 

LUNG CANCER : SMALL-CELL (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)

Topotecan

(von Pawel J, et al.

J Clin Oncol.

1999;17:658-67)

 

 

N= 107

 

 

Topotecan 1.5 mg/m2/d IV over 30 minutes

days 1 – 5

Repeat cycle every 21 days

Leukopenia

Grade III 54.8%

Grade IV 31.7%

Neutropenia

Grade III 18.3%

Grade IV 70.2%

 

Level III 39.4 %

Level IV 2.9 %

Neutropenic Fever 28 %

Neutropenic Sepsis 5 %

Thrombocytopenia 58 %

Nausea 4 %

Fatigue 5 %

Vomiting 2 %

Stomatitis 2 %

Anorexia 1 %

Diarrhea  1 %

Fever 2 %

Days 1 – 5

Level 2

Infectious mortality 4%

Treatment discontinued

due to toxicity in

9 % of patients

RBC transfusions 52%

Dose intensity 76%

Treatment detay

1 week 7 %

Platelet transfusions in

19.6 % of patients

Treatment –related

mortality : 1 patient

acute   respiratory

insufficiency,

1 patient intracerebral

bleeding

 

Topotecan-Paclitaxel

(Jacobs SA, et al,

Proc Am Soc

Clin Oncol,

1999;18:470a.

Abstract 1814)

 

 

N= 29

 

 

Topotecan 1 mg/m2/d IV days 1-5

Paclitaxel 135 mg/m2 IV over 24 hr day 5

Repeat cycle every 28 days

Primary prophylaxis with G-CSF

Appropriate premedications listed in Section 2,

Commonly Used Premedicaiton Regimens

Grade IV 96%

 

 

Neutropenic Fever

%  of cycles

Thrombocytopenia

(Grade IV 0 18%  of cycles

Allergic Reaction * 7 %

Cardiac Dysrhythmia * 3%

 

 

Grade unknown

 

 

Days 1 – 4 –

Level 2

Day 5 –

Level 3

Septic death  3 %