Effect of timing of postoperative chemotherapy on survival of dogs with osteosarcoma

After excision of primary tumors, initiation of chemotherapy for micrometastases is often delayed for 2 to 4 weeks to permit patient recovery and early healing of the surgical wound. However, studies using murine tumors have indicated that removal of a primary tumor may cause increased cell proliferation within micrometastases during the first 7 to 10 days after surgery, potentially rendering the micrometastases more susceptible to chemotherapy. Clinical trials assessing the value of early postoperative initiation of chemotherapy for human breast carcinoma have yielded conflicting results. Osteosarcoma of dogs is a naturally occurring model for human tumors likely to have micrometastases at the time of diagnosis.

Before surgery, 102 dogs with osteosarcoma were randomized to receive cisplatin and doxorubicin chemotherapy beginning either 2 days or 10 days after amputation. Survival analysis was performed for each treatment group and for a historic control group comprised of 162 dogs treated by amputation alone.

Median survival times for dogs treated by amputation alone and for dogs receiving chemotherapy beginning 2 or 10 days after surgery were 5.5, 11.5, and 11.0 months, respectively. Survival was significantly longer for each of the two groups of dogs receiving chemotherapy than for control dogs (P < 0.0001). There was no significant difference in survival between treatment groups (P = 0.727).

These results do not disprove the theory that removal of a primary tumor alters the growth kinetics of metastases, but do imply that there is no substantial advantage to early postoperative initiation of adjuvant chemotherapy for spontaneous tumors of large species.