Allison Gandey

June 06, 2007

June 6, 2007 (Chicago) — Pfizer's experimental drug axitinib may offer patients with advanced thyroid cancer who have not responded to previous therapies such as surgery and radioactive iodine a new alternative. The development was presented here at the American Society of Clinical Oncology 43rd Annual Meeting. The oral drug is an inhibitor of vascular endothelial growth factor 1, 2, and 3 and is being proposed as an alternative to injectable doxorubicin.

"The advantages are profound," lead investigator Ezra Cohen, MD, from the University of Chicago, in Illinois, told Medscape. "We have a drug here that appears to be more active than doxorubicin and appears to be better tolerated." He added that no new drug has been approved in thyroid cancer for more than 30 years. Patients who do not do well on standard therapy have an estimated 30% 5-year survival.

Presentation attendees congratulated Dr. Cohen on the data. Dean Bajorin, MD, from Memorial Sloan-Kettering Cancer Center, in New York, and moderator of a press conference outlining the findings, agreed that axitinib does appear to offer substantial antitumor activity.

Also discussing the results at the meeting, Barbara Burtness, MD, from the Fox Chase Cancer Center, in Philadelphia, Pennsylvania, said that the study provides more than enough impetus to continue the trial.

In this phase 2, single-group, multicenter trial, the researchers followed 60 patients with advanced thyroid cancer. All patients were refractory to conventional therapy. "What was most impressive to us were the partial response rates," Dr. Cohen told reporters.

Best Response Evaluation Criteria in Solid Tumors

Response
Number
Percentage
Partial response
18 months
30
Stable disease ( > 16 weeks)
25
42
Number with any tumor shrinkage
23
38
No response
17
28
Progression
7
12
Indeterminate or unknown
10
17

At least half of the patients did not have progression of disease after a year and a half. Response assessments for the study are ongoing.

Axitinib was administered at 5-mg doses given as a pill twice a day. Dr. Cohen told Medscape that about a third of the patients required a dose adjustment due to toxicities. In such cases, doses were changed to 4 mg, or in some instances, 3 mg. "The majority of patients can stay on the drug," Dr. Cohen said, "only 5 of 60 of the patients had to come off axitinib because of toxicities and 1 of those patients did so voluntarily." In some instances, patients have already been on therapy for 2 years. "It's certainly quite feasible to administer axitinib for that length of time."

Axitinib was well tolerated in the trial, with manageable toxicities. The most common adverse events were considered typical of those observed in other trials of similar vascular endothelial growth factor receptors.

Most Common Treatment-Related Adverse Effects
Adverse Event
Any Grade, n (%)
Grade 3 or More, n (%)
Fatigue
30 (50)
3 (5)
Diarrhea
28 (47)
2 (3)
Stomatitis or mucositis
26 (43)
0
Nausea
19 (32)
0
Proteinuria
23 (40)
4 (7)
Hypertension
17 (28)
7 (12)

"I think we're entering a new age of treatment for patients who have advanced thyroid cancer who failed conventional therapy," Dr. Cohen said. He suggests that the current option of doxorubicin is highly toxic "and is likely to be minimally effective." A global trial testing axitinib in doxorubicin-refractory thyroid cancer is ongoing.

American Society of Clinical Oncology 43rd Annual Meeting: Abstract 6008. Presented June 2, 2007.

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