RENAL CELL CANCER

GENITOURINARY : RENAL CELL 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)

Interferon alfa-2°

(Motzer RJ, et al.

J Clin Oncol.

2000;18:2972-80)

N = 145

Interferon alfa-2a 3 MU SQ daily,

Escalated by 3 MU increments every

7 days, as tolerated to a maximum dose

of 9 MU SQ daily

Appropriate premedications listed in Section 2,

Commonly Used premedicatrion Regimens

Neutropenia

Grade III 3%

Leukopenia

Grade III 7%

Grade III-IV 11%

Thrombocytopenia

(Grade III) 1%

Gastrointestinal

(Grade III) 13%

Altered Mood

(Grade III) 3%

Neurologic Toxicity 3%

Cardiac Toxicity 5%

Level 1

Interferon alfa-2a

(Negrier S, et al.

N Engl J Med.

1998;338:1272-78)

N = 147

Interferon alfa-2a 18 MU SQ

TIW × 10 weeks (induction) then

× 13 additional weeks (maintenance)

Appropriate premedications listed in Section 2,

Commonly Used Premedicatrion Regimens

Leukopenia 0.7%

Grade III-IV 6%

Fever 5%

Nausea/Vomiting 5%

Pulmonary Symptoms 3%

Increased AST/ALT 3%

Weight Loss 6%

Level 1

Interferon alfa +

Aldesleukin

(Negreir S, et al.

N Engi J Med.

1998;338:1272-78)

N = 140

Aldesleukin 18 MU/m²/d as an IV

continuous infusion × 5 days

interferon alfa-2a 6 MU SQ TIW

Treatment consists of 2 induction cycles

and 4 maintenance cycles, with a

3-week rest period between cycles

An induction cycle consists of two 5-day

courses, separated by a 6-day rest period;

aldesleukin is given during the two

induction cycles and during each

maintenance cycle

Appropriate premedications listed in Section 2,

Commonly Used Premedicatrion Regimens

Leukopenia 2%

Grade III-IV 16%

Infection 9%

Fever 56%

Hypotension Resistant

to Vasopressors 67%

Nausea/Vomiting 31%

Diarrhea 25%

Pulmonary Symptoms 15%

Renal Symptoms 16%

Neurologic Symptoms 14%

Increased AST/ALT 11%

Cutaneous Signs 14%

Cardiac Signs 6%

Thrombocytopenia 7%

Increased Creatinine 5%

Hyperbilirubinemia 2%

Days 1-5

(aldesleukin

days)―

level 3

GENITOURINARY : RENAL CELL 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)

Aldesleukin―

High-Dose

(Fyfe G, et al.

J Clin Oncol.

1995;13:688-96)

N = 255

Aldesleukin 600,000 or 720,000 IU/kg IV

over 15 minutes every 8 hours × 14 doses

Repeat after a 9-day rest period

Appropriate premedication listed in Section 2,

Commonly administered in an ICU setting

Grade III-IV 18%

Sepsis 6%

Fever and/or Chills 24%

Oliguria/Anuria 46%

Mental Status

Changes 28%

Nausea/Vomiting 25%

Diarrhea 22 %

Hyperbilirubinemia 21%

Thrombocytopenia 21 %

Dyspnea 17%

Hypotension 74%

Elevated BUN/

Creatinine 14%

Increased AST/ALT 105

Cardiac Toxicity 9 %

Increased Alkaline

Phosphatase 8 %

Acidosis 6%

Asthenia 4%

Pruritus 4%

Stomatitis 4%

Gastrointestinal

Bleeding 4 %

Level 3

4% died of treatment-

related toxicity

Life-threatening sepsis

occurred in 2%

of patients

Toxicities are rapidly

reversible upon

cessation of therapy

Aldesleukin―

Low-Dose Infusional

(Negrier S, et al.

N Engl J Med.

1998;338:1272-78)

N = 138

Aldesleukin 18 MU/m²/d as an IV

continuous infusion × 5 days

Treatment consists of 2 induction cycles and

4 maintenance cycles, with a 3-week rest

period between cycles

An induction cycle consists of two 5-day

courses, separated by a 6-day rest period

Appropriate premedication listed in Section 2,

Commonly Used Premedication Regimens

Leukopenia 0.7%

Grade III-IV 17%

Infection 8 %

Fever 43 %

Hypotension Resistant

to Vasopressors 68%

Nausea/Vomiting 34%

Diarrhea 28 %

Pulmonary Symptoms 16%

Renal Symptoms 15%

Neurologic Symptoms12%

Increased AST/ALT 11 %

Cutaneous Signs 10%

Cardiac Signs 12 %

Thrombocytopenia 4%

Increased Creatinine 4%

Weight Loss 2%

GENITOURINARY : RENAL CELL 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)

Aldesleukin-

Low-Dose SQ

(Tourani JM, et al,

Ann Oncol.

1996;7:525-28)

N= 39

Induction Phase

Weeks 1 and 6 :

Aldesleukin

MU SQ twice daily x 5 consecutive days

Weeks 2, 3, 4, 7, 8, and 9 :

Aldesleukin

9 MU SQ twice daily on days 1 and 2, then

9 MU SQ daily on days 3- 5

Week 5:

Rest period

Maintenance phase begins after

2-week rest period

Maintenance phase

Week 1;

Aldesleukin

9 MU SQ twice daily x 5 consecutive days

Weeks 2-4:

Aldesleukin

9 MU SQ twice daily days 1, 2, then

9 MU SQ daily on days 3-5

Cycles are repeated every 7 weeks for a

Maximum of cycles

Appropriate premedications listed in Section 2,

Commonly Used Premedication Regimens

WHO Toxicity :

Infection (Grade III) 2.6 %

Fever 13%

Asthenia (Grade III) 10 %

Anorexia (Grade III) 8 %

Neuropsychiatric Symptoms

(Grade III) 8%

Cholestasis (Grade III) 5%

Nausea/Vomiting

(Grade III) 2.6 %

Injection-Site Reaction

(Grade III) 2.6 %

Stiffness (Grade III) 2.6 %

Level 1

No patient developed

Grade III-IV hemo-

dynamic or renal

toxicity