Pfizer Limited

6.1 – List of excipients: Addition of the sentence ‘hydrochloric acid (for ph adjustment) used for the product in polypropylene vials’

6.3 – Shelf-Life: Information for polypropylene (plastic) vials

6.4 – Special precautions for storage: Addition of the sentence ‘products in glass vials and polypropylene vials’ and ‘store below 25 degrees C’

6.5- Nature and content of Container: Addition of information on pack sizes for glass and polypropylene vials.

6.6-Instructions for use and handling, and disposal (if applicable), under ‘preparation for the intravenous infusion administration section’ there is a replacement of dextrose with ‘glucose’ and a paragraph describing the instructions for use in more detail to be consistent with the SPC

Section 4.1 paragraph been add.

CAMPTO in combination with cetuximab is indicated for the treatment of patients with epidermal growth factor receptor (EGFR)-expressing metastatic colorectal cancer after failure of irinotecan-including cytotoxic therapy.

Section 4.2 Paragraph been added.

Under “In combination therapy (for previously untreated patient):”

For the posology and method of administration of concomitant cetuximab, refer to the product information for this medicinal product.

Under “Dosage adjustments:”

Recommendations for dose modifications of cetuximab when administered in combination with irinotecan must be followed according to the product information for this medicinal product

Section 4.3. Paragraph been added

For additional contraindications of cetuximab, refer to the product information for this medicinal product.

Section 4.5  Paragraph been added

There is no evidence that the safety profile of irinotecan is influenced by cetuximab or vice versa.

Section 4.8. Paragraph been added

Under “Other gastrointestinal disorders”

Rare cases of symptomatic or asymptomatic pancreatitis have been associated with irinotecan therapy

Section 5.1 Section been added

In combination with cetuximab:

The efficacy of the combination of cetuximab with irinotecan was investigated in two clinical studies. A total of 356 patients with EGFR-expressing metastatic colorectal cancer who had recently failed irinotecan-including cytotoxic therapy and who had a minimum Karnofsky performance status of 60, but the majority of whom had a Karnofsky performance status of 80 received the combination treatment.

EMR 62 202-007: This randomised study compared the combination of cetuximab and irinotecan (218 patients) with cetuximab monotherapy (111 patients).

IMCL CP02-9923: This single arm open-label study investigated the combination therapy in 138 patients.

The efficacy data from these studies are summarised in the table below:

CI = confidence interval, DCR = disease control rate (patients with complete response, partial response, or stable disease for

at least 6 weeks), ORR = objective response rate (patients with complete response or partial response), OS = overall survival

time, PFS = progression-free survival

The efficacy of the combination of cetuximab with irinotecan was superior to that of cetuximab monotherapy, in terms of objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS). In the randomised trial, no effects on overall survival were demonstrated (hazard ratio 0.91, p = 0.48).

Pharmacokinetic/Pharmacodynamic data

The intensity of the major toxicities encountered with CAMPTO (e.g., leukoneutropenia and diarrhoea) are related to the exposure (AUC) to parent drug and metabolite SN-38. Significant correlations were observed between haematological toxicity (decrease in white blood cells and neutrophils at nadir) or diarrhoea intensity and both irinotecan and metabolite SN-38 AUC values in monotherapy.

Section 10 changed from February 2005 to May 2006