You are here: Home: LCU 4 | 2006 : Thomas E Stinchcombe, MD

Tracks 1-12

Track 1 Introduction Track 2 Clinical trial experience with nanoparticle albumin-bound (nab) paclitaxel in lung cancer Track 3 Potential clinical advantages of nab paclitaxel for lung cancer Track 4 Resolution of neuropathy with nab versus standard paclitaxel formulation Track 5 Scheduling of nab paclitaxel in the treatment of lung cancer Track 6 Clinical development of nab paclitaxel for lung cancer Track 7 CALGB-9633 trial of adjuvant carboplatin/paclitaxel for Stage IB disease Track 8 Clinical trial experience with adjuvant carboplatin/docetaxel Track 9 Incorporating bevacizumab into adjuvant clinical trials Track 10 Clinical questions in the treatment of Stage III NSCLC Track 11 Incorporating multikinase inhibitors into lung cancer clinical trials Track 12 Side effects and tolerability of sunitinib in patients with lung cancer

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Track 2

DR STINCHCOMBE: We have some significant Phase II trials. One study, presented by Mike Hawkins, used carboplatin in combination with nab paclitaxel. It was a cohort design in which approximately 25 patients were enrolled sequentially in each cohort with the dose of nab paclitaxel escalating from 225 to 340 mg/m² every three weeks (Hawkins 2006).

All cohorts showed an overall response rate of approximately 29 percent, and an additional 15 percent of patients had stable disease (4.1). The combination of carboplatin and nab paclitaxel appeared to be relatively well tolerated. Particularly, the rate of myelosuppression was low (Hawkins 2006).

In addition, a single-agent nab paclitaxel trial for patients with an ECOG performance status of zero or one was published in the Annals of Oncology by Dr Mark Green. That trial showed a median progression-free survival of approximately six months and a median survival of approximately 11 months (Green 2006; [4.2]).

That’s significant because that’s the progression-free and overall survival we generally see with double-agent chemotherapy regimens. These are promising data.

Track 3

DR STINCHCOMBE: The Phase III trial for patients with breast cancer showed a lower rate of Grade IV neutropenia with nab paclitaxel, which was statistically significant (Gradishar 2006).

Obviously, patients with lung cancer often have cardiopulmonary disease. Because febrile neutropenia could be potentially life threatening, a lower rate of myelosuppression would be a significant advantage.

We are also intrigued by the increased efficacy in the breast cancer literature, and we want to see if that may exist in non-small cell lung cancer.

The other avenue we’re interested in exploring is that of the patient with small cell lung cancer. In our Phase I trial, we saw some nice responses in patients who had been previously treated for small cell lung cancer. The advantage of the combination of carboplatin and nab paclitaxel for patients with small cell lung cancer would be a reduction in febrile neutropenia.

Our current regimen of cisplatin/irinotecan has a significant incidence of febrile neutropenia of approximately five percent. If we can administer carboplatin/nab paclitaxel every three weeks, it would be a significant improvement over cisplatin/etoposide or carboplatin/etoposide on days one through three, in terms of patient convenience.

DR LOVE: How much of an advantage is the avoidance of premedications and allergic reactions with nab paclitaxel?

DR STINCHCOMBE: That’s a significant advantage. We know hypersensitivity reactions occur with the standard formulation of paclitaxel in about three percent of patients. This can be a significant event, and it can be life threatening.

Premedications also make it somewhat cumbersome in that some patients have diabetes and develop hyperglycemia related to the dexamethasone. Also, the standard formulation of paclitaxel requires a three-hour infusion, whereas nab paclitaxel only requires a 30-minute infusion (4.3). Nab paclitaxel could make the visit more efficient for the patient.

Track 5

DR STINCHCOMBE: Nab paclitaxel may be studied in several areas of development in non-small cell and small cell lung cancer.

Interest has arisen in performing a Phase III trial comparing it to the standard formulation of paclitaxel to determine whether it may be superior. That probably would be done in combination with carboplatin. It may be superior in terms of efficacy or toxicity, which would be a valuable step forward.

A current Phase II trial evaluating carboplatin, nab paclitaxel and bevacizumab is headed by Craig Reynolds. ECOG-E4599 showed a statistically significant increase in the incidence of neutropenia with carboplatin, paclitaxel and bevacizumab (Sandler 2005).

I personally don’t believe it was a clinically significant difference, but the combination of carboplatin, nab paclitaxel and bevacizumab may reduce the risk.

If we’re going to develop a platinum-based combination with bevacizumab, a multitargeted TKI and potentially a fourth agent, we need to minimize the toxicity with our platinum platform so we don’t have an increased rate of neutropenia or other complications.

Therefore, if we were to develop a four-drug therapy for non-small cell lung cancer, it might benefit us to have a taxane that is better tolerated, with less myelosuppression.

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