Camptosar: Package Insert and Label Information

CAMPTOSAR- irinotecan hydrochloride injection, solution
Pharmacia & Upjohn Company LLC

1 INDICATIONS AND USAGE

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CAMPTOSAR is indicated as a component of first-line therapy in combination with 5-fluorouracil (5-FU) and leucovorin (LV) for patients with metastatic carcinoma of the colon or rectum.

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CAMPTOSAR is indicated for patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following initial fluorouracil-based therapy.

2 DOSAGE AND ADMINISTRATION

2.1 Colorectal Cancer Combination Regimens 1 and 2

Administer CAMPTOSAR as a 90-minute intravenous infusion followed by LV and 5-FU. The currently recommended regimens are shown in Table 1.

A reduction in the starting dose by one dose level of CAMPTOSAR may be considered for patients with any of the following conditions: prior pelvic/abdominal radiotherapy, performance status of 2, or increased bilirubin levels. Dosing for patients with bilirubin >2 mg/dL cannot be recommended because there is insufficient information to recommend a dose in these patients.

Table 1. Combination-Agent Dosage Regimens and Dose Modifications *

* Dose reductions beyond Dose Level –2 by decrements of ≈ 20% may be warranted for patients continuing to experience toxicity. Provided intolerable toxicity does not develop, treatment with additional cycles may be continued indefinitely as long as patients continue to experience clinical benefit. † Infusion follows bolus administration.
Regimen 1 6-wk cycle with bolus 5-FU/LV (next cycle begins on day 43)	CAMPTOSAR LV5-FU	125 mg/m2 intravenous infusion over 90 minutes, days 1,8,15,2220 mg/m2 intravenous injection bolus, days 1,8,15,22500 mg/m2 intravenous injection bolus, days 1,8,15,22
		Starting Dose & Modified Dose Levels (mg/m2)
		Starting Dose	Dose Level -1	Dose Level -2
	CAMPTOSAR	125	100	75
	LV	20	20	20
	5-FU	500	400	300
Regimen 2 6-wk cycle with infusional 5-FU/LV(next cycle begins on day 43)	CAMPTOSAR	180 mg/m2 intravenous infusion over 90 minutes, days 1,15,29
	LV	200 mg/m2 intravenous infusion over 2 hours, days 1,2,15,16,29,30
	5-FU Bolus	400 mg/m2 intravenous injection bolus, days 1,2,15,16,29,30
	5-FU Infusion †	600 mg/m2 intravenous infusion over 22 hours, days 1,2,15,16,29,30
		Starting Dose & Modified Dose Levels (mg/m2)
		Starting Dose	Dose Level -1	Dose Level -2
	CAMPTOSAR	180	150	120
	LV	200	200	200
	5-FU Bolus	400	320	240
	5-FU Infusion †	600	480	360

Dosing for patients with bilirubin >2 mg/dL cannot be recommended because there is insufficient information to recommend a dose in these patients [see Warnings and Precautions (5.10), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

Dose Modifications

Based on recommended dose levels described in Table 1, Combination Regimens of CAMPTOSAR and Dose Modifications, subsequent doses should be adjusted as suggested in Table 2, Recommended Dose Modifications for Combination Regimens. All dose modifications should be based on the worst preceding toxicity.

Table 2. Recommended Dose Modifications for CAMPTOSAR/5-Fluorouracil (5-FU)/Leucovorin (LV) Combination Schedules

Patients should return to pre-treatment bowel function without requiring antidiarrhea medications for at least 24 hours before the next chemotherapy administration. A new cycle of therapy should not begin until the granulocyte count has recovered to ≥1500/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 therapy.
Toxicity NCI CTC Grade * (Value)	During a Cycle of Therapy	At the Start of Subsequent Cycles of Therapy †
* National Cancer Institute Common Toxicity Criteria (version 1.0) † Relative to the starting dose used in the previous cycle ‡ Pretreatment § Excludes alopecia, anorexia, asthenia
No toxicity	Maintain dose level	Maintain dose level
Neutropenia
1 (1500 to 1999/mm3)	Maintain dose level	Maintain dose level
2 (1000 to 1499/mm3)	↓ 1 dose level	Maintain dose level
3 (500 to 999/mm3)	Omit dose until resolved to ≤ grade 2, then ↓ 1 dose level	↓ 1 dose level
4 (<500/mm3)	Omit dose until resolved to ≤ grade 2, then ↓ 2 dose levels	↓ 2 dose levels
Neutropenic fever	Omit dose until resolved, then ↓ 2 dose levels
Other hematologic toxicities	Dose modifications for leukopenia or thrombocytopenia during a cycle of therapy and at the start of subsequent cycles of therapy are also based on NCI toxicity criteria and are the same as recommended for neutropenia above.
Diarrhea
1 (2–3 stools/day > pretx ‡)	Delay dose until resolved to baseline, then give same dose	Maintain dose level
2 (4–6 stools/day > pretx)	Omit dose until resolved to baseline, then ↓ 1 dose level	Maintain dose level
3 (7–9 stools/day > pretx)	Omit dose until resolved to baseline, then ↓ 1 dose level	↓ 1 dose level
4 (≥10 stools/day > pretx)	Omit dose until resolved to baseline, then ↓ 2 dose levels	↓ 2 dose levels
Other nonhematologic toxicities §
1	Maintain dose level	Maintain dose level
2	Omit dose until resolved to ≤ grade 1, then ↓ 1 dose level	Maintain dose level
3	Omit dose until resolved to ≤ grade 2, then ↓ 1 dose level	↓ 1 dose level
4	Omit dose until resolved to ≤ grade 2, then ↓ 2 dose levels	↓ 2 dose levels
	For mucositis/stomatitis decrease only 5-FU, not CAMPTOSAR	For mucositis/stomatitis decrease only 5-FU, not CAMPTOSAR.

2.2 Colorectal Single Agent Regimens 1 and 2

Administer CAMPTOSAR as a 90-minute intravenous infusion. The currently recommended regimens are shown in Table 3.

A reduction in the starting dose by one dose level of CAMPTOSAR may be considered for patients with any of the following conditions: prior pelvic/abdominal radiotherapy, performance status of 2, or increased bilirubin levels. Dosing for patients with bilirubin >2 mg/dL cannot be recommended because there is insufficient information to recommend a dose in these patients.

Table 3. Single-Agent Regimens of CAMPTOSAR and Dose Modifications

* Subsequent doses may be adjusted as high as 150 mg/m 2 or to as low as 50 mg/m 2 in 25 to 50 mg/m 2 decrements depending upon individual patient tolerance. † Provided intolerable toxicity does not develop, treatment with additional cycles may be continued indefinitely as long as patients continue to experience clinical benefit. ‡ Subsequent doses may be adjusted as low as 200 mg/m 2 in 50 mg/m 2 decrements depending upon individual patient tolerance.
Regimen 1 (weekly) *	125 mg/m2 intravenous infusion over 90 minutes, days 1,8,15,22 then 2-week rest
	Starting Dose and Modified Dose Levels † (mg/m2)
	Starting Dose	Dose Level -1	Dose Level -2
	125	100	75
Regimen 2 (every 3 weeks) ‡	350 mg/m2 intravenous infusion over 90 minutes, once every 3 weeks †
	Starting Dose and Modified Dose Levels (mg/m2)
	Starting Dose	Dose Level -1	Dose Level -2
	350	300	250

Dose Modifications

Based on recommended dose-levels described in Table 3, Single-Agent Regimens of CAMPTOSAR and Dose Modifications, subsequent doses should be adjusted as suggested in Table 4, Recommended Dose Modifications for Single-Agent Schedules. All dose modifications should be based on the worst preceding toxicity.

Table 4.Recommended Dose Modifications For Single-Agent Schedules *

A new cycle of therapy should not begin until the granulocyte count has recovered to ≥1500/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.
Worst Toxicity NCI Grade † (Value)	During a Cycle of Therapy	At the Start of the Next Cycles of Therapy (After Adequate Recovery), Compared with the Starting Dose in the Previous Cycle *
	Weekly	Weekly	Once Every 3 Weeks
* All dose modifications should be based on the worst preceding toxicity † National Cancer Institute Common Toxicity Criteria (version 1.0) ‡ Pretreatment § Excludes alopecia, anorexia, asthenia
No toxicity	Maintain dose level	↑ 25 mg/m2 up to a maximum dose of 150 mg/m2	Maintain dose level
Neutropenia
1 (1500 to 1999/mm3)	Maintain dose level	Maintain dose level	Maintain dose level
2 (1000 to 1499/mm3)	↓ 25 mg/m2	Maintain dose level	Maintain dose level
3 (500 to 999/mm3)	Omit dose until resolved to ≤ grade 2, then ↓ 25 mg/m2	↓ 25 mg/m2	↓ 50 mg/m2
4 (<500/mm3)	Omit dose until resolved to ≤ grade 2, then ↓ 50 mg/m2	↓ 50 mg/m2	↓ 50 mg/m2
Neutropenic fever	Omit dose until resolved, then ↓ 50 mg/m2 when resolved	↓ 50 mg/m2	↓ 50 mg/m2
Other hematologic toxicities	Dose modifications for leukopenia, thrombocytopenia, and anemia during a cycle of therapy and at the start of subsequent cycles of therapy are also based on NCI toxicity criteria and are the same as recommended for neutropenia above.
Diarrhea
1 (2–3 stools/day > pretx ‡)	Maintain dose level	Maintain dose level	Maintain dose level
2 (4–6 stools/day > pretx)	↓ 25 mg/m2	Maintain dose level	Maintain dose level
3 (7–9 stools/day > pretx)	Omit dose until resolved to ≤ grade 2, then ↓ 25 mg/m2	↓ 25 mg/m2	↓ 50 mg/m2
4 (≥10 stools/day > pretx)	Omit dose until resolved to ≤ grade 2 then ↓ 50 mg/m2	↓ 50 mg/m2	↓ 50 mg/m2
Other nonhematologic § toxicities
1	Maintain dose level	Maintain dose level	Maintain dose level
2	↓ 25 mg/m2	↓ 25 mg/m2	↓ 50 mg/m2
3	Omit dose until resolved to ≤ grade 2, then ↓ 25 mg/m2	↓ 25 mg/m2	↓ 50 mg/m2
4	Omit dose until resolved to ≤ grade 2, then ↓ 50 mg/m2	↓ 50 mg/m2	↓ 50 mg/m2