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It's very unfortunate that Multiple Drug Resistance (MDR) has occured at this early a stage.

When my Daisy came out of remission the choice of the Oncologist was to try Mitoxantrone+Dacarbazine. Mitoxantrone is a less cardiotoxic analog of Doxorubicin, and also tends to be less effective. The Dacarbazine is added in an attempt to help overcome the glycoprotein pump responsible for MDR. Zofran was needed to control nausea. The treatment had little to no effect.

Next up was Lomustine, which also didn't have an effect, and caused severe bone marrow suppression. Burned up all the remaining doses of Elspar trying to keep the cancer under control while waiting for the bone marrow to recover. In short Lomustine was a disaster. A couple other stories I've heard about Lomustine have also not been too favorable.

Here is a page with the common rescue protocols for canine lymphoma:

Rescue protocols

One of the better protocols on that page is DMAC. The idea is to use drugs where resistance does not involve the MDR glycoprotein pump.

If I had things to do over again, I would be inquiring about the use of 9-aminocamptothecin, which has been shown as a good induction single agent treatment. The 9-AC also is a drug not suspectable to MDR. From the article I read about it, you might have to control nausea with Zofran if Metoclopromide isn't enough. Also causes bone marrow suppression as a main side affect.

The authors of the article concluded: Camptothecin drugs offer a novel therapeutic approach to the treatment of canine lymphoma. The high objective response rate seen in this small group of dogs implies that 9-AC will have utility in the field of veterinary oncology.

If your Vet/oncologist is unfamilar with this drug refer them to:

Journal of Veterinary and Comparative Oncology 1,2, 86-93 2003

Probably your first task is to try to get the cancer under control, and it usually responds well to Elspar for up to 4-5 treatments total. It's a drug you should use sparingly and hold in reserve for later on for emergencies. Then after the latest swelling goes down, you have up to 5 days to decide on which rescue protocol to use.