You are here: Home: LCU 3 | 2006 : Nasser H Hanna, MD

Tracks 1-17

Track 1 Introduction Track 2 Clinical research evaluating erlotinib combined with bevacizumab for patients with performance status II Track 3 Continuation of erlotinib after tumor response and subsequent disease progression Track 4 Benefit of erlotinib in combination with bevacizumab as second-line therapy Track 5 Predictors of response to EGFR inhibitors Track 6 Phase II trial of weekly paclitaxel with bevacizumab for patients with small cell lung cancer Track 7 Potential advantages of nab paclitaxel versus paclitaxel Track 8 Design and results of SWOG-S9504 and SWOG-S0023 Track 9 Hoosier Oncology Phase III trial evaluating docetaxel consolidation for patients with Stage III non-small cell lung cancer (NSCLC) Track 10 Prophylactic use of growth factor support with lung cancer regimens Track 11 Importance of maintaining dose intensity in the adjuvant setting Track 12 Phase II trial combining bevacizumab with chemoradiation therapy for Stage III disease Track 13 Potential role of adjuvant bevacizumab for NSCLC Track 14 Mechanism of action and predictors of response to bevacizumab Track 15 Selection of adjuvant systemic therapy Track 16 Irinotecan/cisplatin versus etoposide/cisplatin for patients with small cell lung cancer Track 17 Differences in response to treatment in Japanese populations

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Track 4

DR HANNA: It’s an important study because once patients are in the second-line setting their survival times are usually very short. The vast majority of patients in this setting do not survive one year.

It’s unacceptable to induce toxicities in this patient population, particularly when the goal is palliation. So a regimen that is well tolerated and effective in this group of patients would be ideal.

In the second-line setting, one would expect the response rate with chemotherapy agents to be about 10 percent, with a median survival time of six to eight months. In the trial combining erlotinib with bevacizumab, the response rate was 20 percent and the median survival time exceeded a year (Herbst 2005; [2.1]).

It was a Phase II, two-institution study, but the results are still remarkable. So I believe it’s appropriate to conduct the randomized Phase III study, the design of which is erlotinib with or without bevacizumab.

The combination appears to be well tolerated because these agents don’t have the same side-effect profiles as chemotherapy drugs. They usually don’t cause nausea, vomiting, alopecia, diarrhea, mucositis, myelosuppression, et cetera.

Track 9

DR HANNA: For the last three and a half years, the Hoosier Oncology Group, in collaboration with US Oncology, has been conducting a Phase III randomized trial (HOG LUN01-24; [2.2]) for patients with Stage IIIA/IIIB disease who have a performance status of zero or one.

All cases are considered unresectable, and they’re all treated with cisplatin and etoposide with chest radiation, just as SWOG has done for years.

After the completion of that therapy — as long as they haven’t experienced disease progression or undue toxicity and they have maintained a performance status of zero, one or two — patients are randomly assigned either to be observed or to receive three cycles of docetaxel.

At ASCO this year, we will be presenting some initial data regarding consolidation therapy. The issues at hand in our patient population are: what percentage of patients were able to be randomly assigned, what percentage of patients who were treated with docetaxel received all three cycles, what percentage needed dose reductions or dose omissions, what percentage required growth factor support, and what were the complication rates of patients, including hospitalization rates, blood transfusion rates and such. These are all important to consider.

A major difference between our trial and the Southwest Oncology Group 9504 trial is that the pulmonary function of patients only had to be an FEV1 (forced expiratory volume in one second) of greater than one liter.

I believe that that represents the smoking lung cancer population to a greater degree than an FEV1 of greater than two liters. In fact, we evaluated our data, and based upon that criteria alone, half of the patients who entered our trial would not have been eligible for the SWOG trial.

I believe patients who have better pulmonary function probably have better cardiac function and are more fit. It’s also important when viewing rates of pneumonitis and late complications of therapy that we understand the baseline pulmonary function of patients. If somebody’s baseline pulmonary function is excellent, they can take some pneumonitis and pulmonary fibrosis.

However, if baseline FEV1 is borderline and you start causing fibrosis, that patient will likely remain on oxygen and be chronically short of breath, which is unpleasant for patients. So with that criteria, our trial will represent a more representative group of patients in the general community.

Track 14

DR HANNA: The regimen that was used in the US Intergroup/NCI Canada study JBR.10 (Winton 2005; [2.3]) was vinorelbine with cisplatin. The large 800-patient ANITA trial (Douillard 2005; [2.3]) also evaluated vinorelbine and cisplatin, so I believe it’s perfectly appropriate to use that regimen.

Also, it’s appropriate to administer etoposide with cisplatin because more than 50 percent of the patients who received chemotherapy on the International Adjuvant Lung Trial received this combination (Arriagada 2004; [2.3]).

My preference is to use docetaxel plus carboplatin because three randomized trials in metastatic disease indicate that docetaxel is a superior drug to vinorelbine.

The first was a second-line trial, which Dr Fossella reported seven years ago, evaluating docetaxel with either ifosfamide or vinorelbine. Docetaxel showed a superior one-year survival compared to vinorelbine.

The second trial was the TAX-326 trial, which Dr Fossella also reported and which led to the registration of docetaxel as first-line therapy for NSCLC.

The control arm on that study administered vinorelbine and cisplatin versus docetaxel and cisplatin. In that study, docetaxel/cisplatin was superior to vinorelbine/cisplatin (Fossella 2003; [2.4]).

The third was a study from Japan, reported at ASCO 2005, observing an elderly group of patients treated with first-line docetaxel versus vinorelbine. Docetaxel was significantly superior to vinorelbine.

I believe docetaxel and cisplatin are better than vinorelbine and cisplatin in the adjuvant setting. Again, vinorelbine/cisplatin and etoposide/cisplatin are reasonable, but I consider our most effective agents to be docetaxel and cisplatin.

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