Table of Contents... Efficacy Clinical Benefit Safety Profile Dosage & Administration Summary Weekly Dosing Once Every 3 Weeks Dosing

Efficacy

Two phase III multicenter, randomized clinical studies confirm significantly improved overall survival with CAMPTOSAR compared with Best Supportive Care (BSC) or 5-FU in patients with metastatic colorectal cancer recurring or progressing after treatment with 5-FU.

SIGNIFICANTLY IMPROVED OVERALL SURVIVAL WITH CAMPTOSAR

Survival with CAMPTOSAR 350 mg/m² once every 3 weeks vs Best Supportive Care

 

Median survival is 41% greater with CAMPTOSAR vs BSC.

Survival with CAMPTOSAR 350 mg/m² once every 3 weeks vs Infusional 5-FU*

 

Median survival is 27% greater with CAMPTOSAR vs 5-FU

Response Rate With CAMPTOSAR 125 mg/m² Weekly Schedule

• Data pooled across 3 phase II studies (N=304) yielded a 15% objective response rate. These studies were designed to evaluate tumor response and do not provide information on actual clinical benefit, such as effects on survival and disease-related symptoms.

AS DEFINED BY A REDUCTION IN DISEASE-RELATED SYMPTOMS

CAMPTOSAR 350 mg/m² once every 3 weeks vs Best Supportive Care

	Clinical benefit was evaluated periodically up to 1 year; data were collected prospectively and analyses defined retrospectively.
	Significantly Longer Time to Onset Of Pain (median, months)	Significantly Longer Time to Weight Loss 5% (median, months)
	Patients evaluated were pain free at baseline.
	Significantly Longer Time to Performance-Status Deterioration (median, months)

CAMPTOSAR 350 mg/m² once every 3 weeks vs Infusional 5-FU

• Measures of clinical benefit were not significantly different.

European Organization For Research And Treatment Of Cancer

QUALITY OF LIFE QUESTIONNAIRE RESULTS

CAMPTOSAR 350 mg/m² once every 3 weeks vs Best Supportive Care

Patients periodically completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).

• The EORTC questionnaire assessed global health status, functional abilities, and symptoms in a series of subscales.
• Global health-status scores were significantly higher for patients treated with CAMPTOSAR than for those on BSC alone (P=.03).
• For functional abilities, patients receiving CAMPTOSAR achieved significantly higher scores in physical (P=.0003) and role functioning (P=.02) compared with those receiving BSC. There was no statistically significant difference in scores of cognitive, emotional, or social functioning.
• Patients receiving CAMPTOSAR reported significantly improved results on the following symptom subscales:

FATIGUE (P=.03) APPETITE LOSS (P=.0007)

CONSTIPATION (P=.03) PAIN (P=.009)

• On remaining symptom subscales, patients receiving BSC reported significantly less diarrhea (P=.01) and no statistically significant difference in insomnia, dyspnea, nausea/vomiting, and financial impact.

CAMPTOSAR 350 mg/m² once every 3 weeks vs Infusional 5-FU

• The EORTC questionnaire did not indicate a statistically significant difference between CAMPTOSAR and 5-FU.

ADVERSE EVENTS

• CAMPTOSAR can induce severe myelosuppression and both early and late forms of diarrhea which may be life threatening; deaths due to sepsis have been reported.

• Cholinergic symptoms (eg, rhinitis, lacrimation, increased salivation, diaphoresis, abdominal cramping, early-onset diarrhea, miosis, and/or flushing) were reported in 47% (350-mg/m² dosage schedule) and 51% (125-mg/m² dosage schedule) of patients during or shortly after the infusion of CAMPTOSAR.
• In the 125-mg/m² weekly dosing trials, 27% of patients were hospitalized as a result of adverse events related to CAMPTOSAR.
• At either dosing schedule, the discontinuation rate due to adverse events was 8%.

MANAGEMENT OF SIDE EFFECTS

Late-Onset Diarrhea (>24 hr after infusion)

• Patients should be instructed to have loperamide available and begin treatment immediately at the first episode of poorly formed or loose stools, or at the earliest onset of more-frequent bowel movements than normal for the patient.
• Patients with severe diarrhea should be carefully monitored and given fluid and electrolyte replacement if they become dehydrated.
• If grade 3 or 4 diarrhea occurs, administration of CAMPTOSAR should be delayed until the patient recovers, and subsequent doses should be decreased.

Loperamide Regimen

Myelosuppression

• Therapy with CAMPTOSAR should be temporarily omitted if neutropenic fever occurs or if absolute neutrophil counts drop below 1,000/mm³.

Nausea and Vomiting

• CAMPTOSAR is emetogenic, and premedication with antiemetics is recommended.

Cholinergic Symptom Management

 

Two Dosage Options Now Available

• 350 mg/m², as a 90-minute infusion, administered once every 3 weeks.
• 125 mg/m² as a 90-minute infusion, administered weekly for 4 weeks, followed by a 2-week rest.

Starting Dosage in Compromised Patients

• Every-3-week schedule: 300 mg/m² if age 70, performance status of 2, or prior pelvic/abdominal radiotherapy.
• Weekly schedule: Consider 100 mg/m² in patients with combined history of prior pelvic/abdominal irradiation and modestly elevated total bilirubin levels (1.0 to 2.0 mg/dL).

Dosage Modifications

• Monitor patients carefully for toxicity and adjust dosage according to full prescribing information.
• For specific toxicity and dosage modification information, please see dosage card.

WEEKLY DOSING

125 mg/m², Weekly x4 CAMPTOSAR^® Injection

 

Recommended Dosage Modifications*
A new course of therapy should not begin until the granulocyte count has recovered to 1,500/mm3, and the platelet count has recovered to 100,000/mm3, and treatment-related diarrhea is fully resolved. Treatment should be delayed 1 to 2 weeks to allow for recovery from treatment-related toxicities. If the patient has not recovered after a 2-week delay, consideration should be given to discontinuing CAMPTOSAR.
Toxicity: NCI Grade(value)	During a Course of Therapy	At the Start of Subsequent Courses of Therapy
No Toxicity	Maintain dosage level	25 mg/m2 to a maximum of 150 mg/m2
Neutropenia
1 (1,500 to 1,999/mm3)	Maintain dosage level	Maintain dosage level
2 (1,000 to 1,499/mm3)	25 mg/m2	Maintain dosage level
3 (500 to 999/mm3)	Omit dosage, then 25 mg/m2 when resolved to = or < grade 2	25 mg/m2
4 (<500/mm3)	Omit dosage, then 50 mg/m2 when resolved to = or < grade 2	50 mg/m2
Neutropenic Fever	Omit dosage, then 50 mg/m2 when resolved	50 mg/m2
Other Hematologic Toxicities	Dosage modifications for leukopenia or thrombocytopenia during a course of therapy and at start of subsequent courses of therapy are also based on NCI Common Toxicity Criteria and are the same as recommended for neutropenia above.
Diarrhea
1 (2-3 stools/day > pretreatment)	Maintain dosage level	Maintain dosage level
2 (4-6 stools/day > pretreatment)	25 mg/m2	Maintain dosage level
3 (7-9 stools/day > pretreatment	Omit dose, then 25 mg/m2 when resolved to = or < grade 2	25 mg/m2
4 (10 stools/day > pretreatment)	Omit dose, then 50 mg/m2 when resolved to = or < grade 2	50 mg/m2
Other Nonhematologic Toxicities
1	Maintain dosage level	Maintain dosage level
2	25 mg/m2	25 mg/m2
3	Omit dose, then 25 mg/m2 when resolved to = or < grade 2	25 mg/m2
4	Omit dose, then 50 mg/m2 when resolved to = or < grade 2	50 mg/m2
* All dosage modifications should be based on the worst preceding toxicity. NCI Common Toxicity Criteria version 2.0, Final 1/30/98, NCI revised 3/23/98. Refers to initial dose used in previous course.

ONCE-EVERY-3-WEEK DOSING

350 mg/m², Once-Every-3-Weeks CAMPTOSAR^® Injection

 

Recommended Dosage Modifications*
A new course of therapy should not begin until the granulocyte count has recovered to 1,500/mm3, and the platelet count has recovered to 100,000/mm3, and treatment-related diarrhea is fully resolved. Treatment should be delayed 1 to 2 weeks to allow for recovery from treatment-related toxicities. If the patient has not recovered after a 2-week delay, consideration should be given to discontinuing CAMPTOSAR.
Toxicity: NCI Grade(value)	At the Start of Subsequent Courses of Therapy
No Toxicity	Maintain dosage level
Neutropenia
1 (1,500 to 1,999/mm3)	Maintain dosage level
2 (1,000 to 1,499/mm3)	Maintain dosage level
3 (500 to 999/mm3)	50 mg/m2
4 (<500/mm3)	50 mg/m2
Neutropenic Fever	50 mg/m2
Other Hematologic Toxicities	Dosage modifications for leukopenia or thrombocytopenia at the start of subsequent courses of therapy are also based on NCI Common Toxicity Criteria and are the same as recommended for neutropenia above.
Diarrhea
1 (2-3 stools/day > pretreatment)	Maintain dosage level
2 (4-6 stools/day > pretreatment)	Maintain dosage level
3 (7-9 stools/day > pretreatment)	50 mg/m2
4 (10 stools/day > pretreatment)	50 mg/m2
Other Nonhematologic Toxicities
1	Maintain dosage level
2	50 mg/m2
3	50 mg/m2
4	50 mg/m2
* All dosage modifications should be based on the worst preceding toxicity. NCI Common Toxicity Criteria version 2.0, Final 1/30/98, NCI revised 3/23/98.

• Significantly longer survival compared to survival with Best Supportive Care or 5-FU.
• Improved clinical benefit (reduction in disease-related symptoms) compared with Best Supportive Care, with significantly longer time to onset of pain, longer time to weight loss 5%, and longer time to performance-status deterioration.
• EORTC QLQ-C30 results demonstrate significantly better results for global health status vs Best Supportive Care and no statistically significant difference vs 5-FU.
• CAMPTOSAR can induce myelosuppression and both early and late forms of diarrhea which may be severe.
• Nausea and vomiting are commonly reported; premedication with antiemetic agents is recommended.

 

© 1999 Pharmacia & Upjohn Company		USX 2030.00 January 1999

 

Full Prescribing Information

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