Tuesday, February 9, 2010

Induction Chemo for Rectal Cancer

This weeks JCO has a randomized phase II study examining induction chemotherapy for rectal cancer. The endpoint was pCR, a reasonable surrogate for clinical outcome.

Randomized phase II studies are always a bit of an enigma to me. They are not powered to show differences between the arms (that would be a phase III), and yet they are randomized. The practical significance is that it is much easier to get these done because the accrual goals are much lower than a true phase III. In this case, the goals of the researchers was to "drop" a less effective arm, i.e. assuming that the better arm would have a pCR rate of 15%, they had 90% power to detect a difference if the worse arm was 10%.

Either way, their results are similar to what has been seen in other induction trials for solid tumors, no differences in the clinically significant disease endpoints. What they did show is better tolerance of the chemotherapy, and thus more exposure to drug. One other thing that is obviously important is to look for the ability to deliver radiation and go to surgery afterwards, which fortunately was no different between the arms.

They conclude that it was reasonable to move onto phase III comparing these approaches.

Link and Abstract:

The optimal therapeutic sequence of the adjuvant chemotherapy component of preoperative chemoradiotherapy (CRT) for patients with locally advanced rectal cancer is controversial. Induction chemotherapy before preoperative CRT may be associated with better efficacy and compliance.

Patients and Methods

A total of 108 patients with locally advanced rectal cancer were randomly assigned to arm A—preoperative CRT with capecitabine, oxaliplatin, and concurrent radiation followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)—or arm B—induction CAPOX followed by CRT and surgery. The primary end point was pathologic complete response rate (pCR).


On an intention-to-treat basis, the pCR for arms A and B were 13.5% (95% CI, 5.6% to 25.8%) and 14.3% (95% CI, 6.4% to 26.2%), respectively. There were no statistically significant differences in other end points, including downstaging, tumor regression, and R0 resection. Overall, chemotherapy treatment exposure was higher in arm B than in arm A for both oxaliplatin (P < .0001) and capecitabine (P < .0001). During CRT, grades 3 to 4 adverse events were similar in both arms but were significantly higher in arm A during postoperative adjuvant CT than with induction CT in arm B. There were three deaths in each arm during the treatment period.


Compared with postoperative adjuvant CAPOX, induction CAPOX before CRT had similar pCR and complete resection rates. It did achieve more favorable compliance and toxicity profiles. On the basis of these findings, a phase III study to definitively test the induction strategy is warranted."

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