Docetaxel as Second-Line Therapy in Advanced NSCLC

MELVILLE, NY—Docetaxel (Taxo-tere) is becoming increasingly important for the second-line treatment of advanced non-small-cell lung cancer (NSCLC), said Jeffrey Crawford, MD, director of Clinical Research, Duke Comprehensive Cancer Center, Duke University.

“I think docetaxel is probably the drug of choice for patients with symptomatic advanced non-small-cell lung cancer who have failed front-line therapy and are still in good health,” he said at North Shore University Hospital’s annual cancer conference, which focused on taxanes and was sponsored by Rhône-Poulenc Rorer.

Two phase II trials of single-agent docetaxel in platinum-resistant or platinum-refractory NSCLC have been reported, he noted. At doses of 100 mg/m2 infused over 1 hour once every 3 weeks, second-line docetaxel elicited partial responses in 14% to 22% of patients and 1-year survival rates of 16% to 41%.

The most important dose-limiting toxicity was neutropenia. A higher incidence of peripheral neuropathy was noted in patients previously treated with cisplatin (Platinol) or carboplatin (Paraplatin) than in chemotherapy-naïve patients.

One of theses trials included a retrospective analysis of controls matched for performance status; compared with these patients, the increases in response rates and 1-year survival with docetaxel appeared to be significant.

As First-Line Chemotherapy

“We used to have no therapy for advanced NSCLC. Now, we have no standard therapy, because there are at least a couple of useful rivals out there,” Dr. Crawford said. He speculated that docetaxel may be useful as front-line therapy, “but we won’t know until more randomized trial data are available.”

In this population, first-line chemotherapy with older agents, such as cisplatin, vindesine, vinblastine, ifos-famide (Ifex), or mitomycin (Muta-mycin), usually produces response rates of 15% to 25% when given singly and 25% to 45% when given in combination.

Response rates are a useful indication of an agent’s potential activity; however, in patients with advanced lung cancer, rates of symptomatic improvement after chemotherapy usually exceed response rates by two- or threefold, Dr. Crawford noted. In advanced lung cancer, survival data are more important than response rates to both clinicians and patients, he said, because survival rates also encompass cases of delayed tumor growth.

One-Year Survival of 30% to 40%

One-year survival rates are 20% to 30% with the older drugs, compared with 10% to 12% with supportive care alone. Regimens containing vinorelbine (Navelbine) or a taxane are clearly superior to the older regimens, he said, because they are producing 1-year survival rates in the 30% to 40% range or higher. “Based on the randomized trials, I would have to say that front-line therapy for advanced NSCLC should include either vinorelbine or a taxane,” Dr. Crawford said.

A prospective, randomized multicen-ter trial compared first-line vinorelbine therapy given weekly with a regimen of fluorouracil plus leucovorin given monthly in patients with advanced NSCLC. The investigators reported a 1-year survival rate of 25% for vinorelbine vs 16% for the combination regimen.

Four phase II trials of first-line docetaxel, 100 mg/m2 every 3 weeks, produced an overall response rate of 27% in patients with advanced disease; the 1- and 2-year survival rates were 39% and 20%, respectively. There is at least one randomized phase III trial showing a taxane (paclitaxel, Taxol) regimen to be superior to older regimens, he noted.

Preliminary results of phase I and II trials combining docetaxel with vinorel-bine have been encouraging in terms of both efficacy and tolerability, he reported. Future studies are needed to determine the optimal dosage regimen and whether the inclusion of G-CSF (Neupo-gen) is necessary for dose intensification.

The Eastern Cooperative Oncology Group reported that single-agent carbo-platin slowed disease progression in stage IV NSCLC significantly longer than did single-agent iproplatin or any of the following combination regimens: vinblas-tine/cisplatin, mitomycin/vinblastine/cisplatin (MVP), or alteration of the MVP regimen and cyclophosphamide/doxorubicin/methotrexate/procarbazine.

Therefore, he said, phase II trials combining carboplatin and docetaxel and phase III trials combining cisplatin and docetaxel are underway in patients with advanced NSCLC. Randomized phase II studies are also evaluating the combination of concomitant radiotherapy, induction therapy with cisplatin or carboplatin, and treatment with either paclitaxel, vinorelbine, or gemcitabine (Gemzar) in this population, he noted.