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Camptosar

Phase II Trial of Irinotecan in Patients with Progressive or Rapidly Recurrent Colorectal Cancer


Rothenberg ML, Eckardt JG, Kuhn GS, et al. Journal of Clinical Oncology. 1996;14(4):1128-1135

A phase II, open-label trial of CAMPTOSAR Injection (irinotecan hydrochloride injection) demonstrated objective tumor response.

Patients

Patients had measurable metastatic colorectal cancer that had recurred or progressed despite prior treatment with one 5-FU-based regimen.

Six-Week Treatment Cycle

Irinotecan 125 to 150 mg/m² IV q week x 4 followed by a 2-week rest continued until tumor progression.

Table 1. - Response to Irinotecan Therapy

Response

Number



Overall response (or)
CR
PR


Median response duration

10/43 (23%)
1/43 (2%)
9/43 (21%)


6 months (range 2 to 13 months)

Measures implemented in this trial substantially reduced the incidence of severe diarrhea.

  1. Use of an irinotecan starting dose of 125 mg/m2/wk
  2. Adoption of a prompt, intensive course of loperamide at the earliest symptoms

Dose Selection

An earlier phase I trial recommended a phase II starting dose of 150 mg/m2/wk. However, the phase II protocol was amended to use a starting dose of 125 mg/m2/wk after an unacceptably high rate of toxicity occurred at the 150-mg/m2; dose.

Table 2. - Severe Diarrhea Observed at
Two Dose Levels

Dose Level

Number Treated

Grade 4 Diarrhea

150 mg/m2/wk

9

4/9 (44%)

125 mg/m²/wk

39

9/39 (23%)

Standardized Management

A standardized approach for prompt and aggressive treatment of late-onset diarrhea (diarrhea that occurred >12 hours after irinotecan administration) was adopted after the first 65 courses were administered to the first 30 patients.

Table 3. - Diarrhea Management Adopted in the Trial

Diarrhea

Management

During or shortly after irinotecan infusion

Atropine 1 mg IV

Late-onset diarrhea
in the initial 65 courses

No standard approach to treatment

Late-onset diarrhea
in the final 145 courses of treatment

At the first sign of diarrhea:
loperamide 4 mg po, followed by 2 mg po q 2 hours (4 mg po q 4 hours at night) until complete resolution lasting 12 hours

Table 4. - Incidence of Grade 4 Late-Onset Diarrhea Following Adoption of the Loperamide Regimen

Irinotecan Dose

Grade 4 Diarrhea

No Standard Regimen

Standardized Loperamide Management

All patients
(150 or 125 mg/m2/wk)
125 mg/m2/wk dose

11/65 courses (17%)

6/42 courses (14%)

7/145 courses (5%)

5/113 courses (4%)

Toxicity

Table 5. - Irinotecan Toxicity by Patient
Worst Grade Experienced During Any Cycle of Therapy (n=48)

Toxicity

No. Pts With grade 3 (%)

No. Pts With grade 4 (%)

Non-hematologic

Abdominal pain

1 (2%)

0

Asthenia

3 (6%)

0

Increased alk phosphatase

2 (4%)

0

Increased bilirubin

3 (6%)

0

Increased creatinine

1 (2%)

1 (2%)

Dehydration

2 (4%)

0

Diarrhea

5 (10%)

13 (27%)

Malaise

1 (2%)

0

Nausea

5 (10%)

0

Vomiting

6 (13%)

2 (4%)

Hematologic

Anemia

4 (8%)

1 (2%)

Leukopenia

10 (2 %)

2 (4%)

Neutropenia

7 (15%)

8 (17%)

Thrombocytopenia

1 (2%)

0

Conclusion

Virtually all patients diagnosed with metastatic colorectal cancer will develop progressive disease following`5-FU-based therapy, thus a need exists for agents with activity in this setting.

See the package insert for full prescribing information.


Pharmacia & Upjohn
Yakult

© 1996 Pharmacia & Upjohn Company


USX 5742.00 August 1996

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