Note:

The majority of patients who relapse after adequate treatment with Roferon-A alone do so within four months of the end of treatment.

- FOLLICULAR NON-HODGKINS LYMPHOMA

Roferon-A prolongs disease-free and progression-free survival when used as adjunctive treatment to CHOP-like chemotherapy regimens in patients with advanced (high tumour burden) follicular non-Hodgkin's lymphoma. However, the efficacy of adjunctive interferon alfa-2a treatment on overall long-term survival of these patients has not yet been established.

Dosage Recommendation:

Roferon-A should be administered concomitantly to a conventional chemotherapy regimen (such as the combination of cyclophosphamide, prednisone, vincristine and doxorubicin) according to a schedule such as 6 million IU/m2 given subcutaneously from day 22 to day 26 of each 28-day cycle.

- ADVANCED RENAL CELL CARCINOMA

COMBINATION WITH VINBLASTINE

Therapy with Roferon-A in combination with vinblastine induces overall response rates of approximately 17-26%, delays disease progression, and prolongs overall survival in patients with advanced renal cell carcinoma.

Dosage recommendation:

Roferon-A should be given by subcutaneous injection at a dose of 3 million IU three times weekly for one week, 9 million IU three times weekly for the following week and 18 million IU three times weekly thereafter. Concomitantly vinblastine should be given intravenously according to the manufacturer's instructions at a dose of 0.1 mg/kg once every 3 weeks.

If the Roferon-A dosage of 18 million IU three times per week is not tolerated the dose may be reduced to 9 million IU three times per week.

Treatment should be given for a minimum of three months, up to a maximum of 12 months or until the development of progressive disease. Patients who achieve a complete response may stop treatment three months after the response is established.

COMBINATION WITH BEVACIZUMAB (AVASTIN)

Dosage recommendations:

9 MIU by subcutaneous injection three times weekly until disease progression or up to 12 months.

The safety and efficacy of Roferon-A therapy after 12 months have not been eva luated.

Roferon-A therapy may be initiated with a lower dose (3 or 6 MIU), the recommended dose of 9 MIU should however be reached within the first 2 weeks of treatment.

If the Roferon-A dosage of 9MIU three times per week is not tolerated, the dosage may be reduced to a minimum dosage of 3 MIU three times per week.

Roferon-A injections are given after completion of the Avastin infusion. For more information on combination use with Avastin, refer to the Avastin SmPC.

- SURGICALLY RESECTED MALIGNANT MELANOMA.

Adjuvant therapy with a low dose of Roferon-A prolongs disease-free interval in patients with no nodal or distant metastases following resection of a melanoma (tumour thickness > 1.5 mm).

Dosage recommendation:

Roferon-A should be administered subcutaneously at a dose of 3 million IU three times a week for 18 months, starting no later than six weeks post surgery. If intolerance develops, the dose should be lowered to 1.5 million IU three times a week.

4.3 Contraindications

 Roferon-A i