A randomized phase II trial comparing every 3-weeks carboplatin/paclitaxel with every 3-weeks carboplatin and weekly paclitaxel in advanced non-small cell lung cancer.

BACKGROUND: The optimal schedule of taxane administration has been an area of active interest in several recent clinical trials. METHODS: To address a pure schedule question, we randomized 161 patients with advanced stage IIIB or IV non-small-cell lung cancer (NSCLC) to either paclitaxel 225 mg/m2 every 3 weeks x 4 cycles or 75 mg/m2/week x 12 (cumulative dose on each arm = 900 mg/m2). Both arms received concurrent carboplatin AUC 6 every 3 weeks x 4 cycles. RESULTS: The two arms were well-balanced in terms of known prognostic factors. The overall response rate and survival outcomes were similar on the two arms. There was significantly more grade 3/4 thrombocytopenia and grade 2-4 anemia on the weekly arm but less severe myalgias/arthralgias and alopecia. No difference in the rates of peripheral neuropathy was observed; however, patients on the every 3 weeks arm reported significantly more taxane therapy-related side-effects on the functional assessment of cancer therapy taxane subscale. CONCLUSIONS: This randomized trial exploring schedule-related issues with carboplatin/paclitaxel confirms the versatility of this regimen.

Brain metastases.

Metastatic tumors to the brain are an increasing cause of morbidity and mortality in patients with systemic cancers. Many new therapies used to treat systemic cancers do not penetrate the central nervous system (CNS) and do not protect patients from the development of brain metastases. Surgery, radiosurgery, and radiation therapy are all used to treat brain metastases. It is in our opinion a mistake to use only one or two of these modalities to the exclusion of other(s). The role of systemic chemotherapy is still limited, due to both the issues of drug delivery caused by the blood brain barrier and to the relative resistance of many of these tumors to chemotherapy. Traditionally, brain metastases have been grouped together regardless of the origin of the tumor and have been treated with a single algorithm. As we encounter more patients for whom treatment of the brain metastases is an important determinant of survival, we must tailor our treatment strategies to individual tumor types. Also, we must recognize differences in each tumor's sensitivity to chemotherapy and radiotherapy and differences in their biology.

The role of induction therapy in the management of resectable non-small cell lung cancer.

BACKGROUND: Combined-modality therapy has become standard for many patients with non-small cell lung cancer. Although surgical resection offers the best chance for long-term survival, the limited number of resectable patients and the presence of occult micrometastatic disease has limited the effectiveness of this modality alone. METHODS: The authors reviewed several trials involving the use of induction chemotherapy in managing resectable non-small cell lung cancer. RESULTS: Extensive phase II experience in patients with stage III disease has confirmed the feasibility of this approach. Unfortunately, heterogeneous patient populations and treatment regimens limit the ability to draw firm conclusions from these trials alone. While the phase III experience has been limited, long-term follow-up is now available suggesting that induction therapy may have a beneficial impact on survival, especially for those patients who can be sufficiently downstaged. Recent phase II trials have included stage III patients who have traditionally been considered inoperable. Although encouraging, the role of surgery after chemoradiotherapy for this population of patients remains undefined. CONCLUSIONS: Results from ongoing randomized trials studying the impact of induction therapy on well-defined patient populations will be necessary before the optimal regimen and patient population can be identified.

Combined-modality therapy in the nonsurgical management of unresectable stage III non-small cell lung cancer.

Combined chemotherapy and radiation for patients with unresectable non-small cell lung cancer has recently been associated with a survival advantage compared with radiation alone; however, despite this apparent improvement in survival, the optimal strategy to combine these two modalities has not yet been defined. Both local tumor control and distant micrometastatic disease remain problems, limiting the curative ability of current combined-modality programs. Over the past year, accelerated radiation schedules have been shown to improve both local tumor control and survival in a selected patient population compared with standard radiotherapy. Some work has centered on the incorporation of novel chemotherapy agents into combined-modality regimens, with encouraging results from phases I and II. Finally, although the benefit for combined-modality therapy has generally been limited to good performance status of patients with minimal weight loss, some data have shown the feasibility of the combined approach in high-risk patient populations. Several ongoing cooperative group phase III trials will help to better define the optimal approach to manage this high-risk patient population.