Impact of adjuvant chemotherapy in stage IB non-small-cell lung cancer: an analysis of 112 consecutively treated patients.

PURPOSE: The impact of adjuvant chemotherapy (CT) in the management of radically resected stage IB non-small cell lung cancer (NSCLC) is highly debated. The aim of this study was to evaluate the outcome of this category of patients treated at our institution. METHODS: We retrospectively analysed the survival data of patients with pathologic stage IB NSCLC, who received at least 1 cycle of adjuvant CT. CT was planned to be platinum based and to be delivered for 6 cycles. RESULTS: One hundred and twelve consecutively treated patients were evaluated. PATIENT CHARACTERISTICS: median age 60 years, median tumor diameter 4 cm, 87% underwent lobectomy and 13% pneumonectomy, 58% had visceral pleural involvement (VPI). After a median follow up of 46 months, the estimated 5-year disease-free (DFS) and overall survival (OS) rates were 68% and 77%, respectively. The mean number of CT cycles was 5.2 (range 3-6), with 82% of patients receiving ≥ 5 cycles. The median cisplatin dose intensity (DI) was 22 mg/m(2)/week, and the relative DI was 85%. Median total cisplatin (CDDP) dose/patient was 416 mg/m(2). A total of 31 (27.6%) relapses were recorded, of which 81% were distant. Multivariate analysis showed no significant interaction between overall survival and the following variables: gender, type of surgery, histology, tumor volume, VPI. CONCLUSION: Our results compare favorably with the historical data evaluating the outcome of stage IB patients treated by surgery alone in a customary medical setting. Overall, our data support the use of adjuvant CT in stage IB NSCLC patients.

Adjuvant therapy with aromatase inhibitors in postmenopausal, estrogen receptor- positive breast cancer patients: upfront or sequential?

For decades tamoxifen (TAM) has been the mainstay hormonal treatment for estrogen receptor positive (ER+) breast cancer patients. Nevertheless, during the last years, for postmenopausal women particularly, the third generation aromatase inhibitors (AI) became the preferred alternative. The results of the randomized trials showed that AI were superior to TAM in terms of efficacy, and were accompanied by a different but fairly convenient side effects profile. Subsequently, all updated guidelines recommend the use of AI in the adjuvant setting for this category of patients, either upfront, following 2-3 years of TAM or as extended adjuvant therapy, after 5 years of TAM. However, no consensus has been reached regarding the best strategy to be used, and the expert opinion is divided, based on the available evidence. The controversial aspect of whether AI should be used upfront or following 2-3 years of TAM is further detailed in this manuscript, and some useful recommendations are provided in order to facilitate the decision-making process during the current clinical practice.

Controversies around the use of monoclonal antibodies in the treatment of advanced non-small cell lung cancer.

First line combination chemotherapy (CT) using platinum-based doublets is established as a standard of care for advanced non-small cell lung cancer (NSCLC). Nevertheless, no significant advances have been recorded during the last years in this field. Therefore, there is a wide consensus among physicians that a plateau has already been reached with this strategy. Targeted therapy using tyrosine-kinase inhibitors (TKIs) and monoclonal antibodies emerged as a new field of development in the NSCLC therapeutics. Recently, the results of the phase III trials testing antibodies against vascular endothelial growth factor-VEGF (bevacizumab) and epidermal growth factor receptor-EGFR (cetuximab) challenged the paradigm of the platinum doublets as a gold standard in advanced NSCLC. Their appearance was enthusiastically commended both by patients and the oncological community. However, all medical oncologists have the responsibility to carefully analyze the real benefits of these new agents, to balance the advantages against the implicit risks of therapy and to make the decision having in mind the best interest of their patients. Last but not least, the associated health economic burden should also be considered. This paper addresses some issues related to the use of cetuximab and bevacizumab in advanced NSCLC. The main controversial aspects regarding patient selection, the real benefit of therapy, the molecular and clinical predictors, and the impact of other independent variables are carefully examined and presented. Due to many unsolved questions, no definite conclusions can be supported. The final decision about the optimal use of these agents is left to the clinical judgment of each treating physician.

Compliance with adjuvant chemotherapy in non-small cell lung cancer. The experience of a single institution evaluating a cohort of 356 patients.

PURPOSE: To evaluate the patient compliance with adjuvant chemotherapy (CT) following radical surgery for non-small cell lung cancer (NSCLC), and to identify the potential confounding factors affecting this particular aspect. PATIENTS AND METHODS: We retrospectively evaluated a series of 356 consecutively treated NSCLC patients at a single institution during 1994-2003. All patients had macroscopic and microscopic radical resection of the primary tumor, with or without mediastinal node dissection or sampling, had received at least one adjuvant CT cycle, with or without postoperative irradiation (RT). CT was planned to be believed for 6 cycles. The following schedules were used: cisplatin (CDDP) 60 mg/m(2), cyclophosphamide 600 mg/m(2) and epirubicin 60 mg/m(2) on day 1 every 21 days (16%);etoposide 120 mg/m(2) and CDDP 30 mg/m(2), on days 1-3, every 21 days (68%); other platinum-based doublets (16%). A multivariate analysis, for a target of 4 and 6 cycles was performed in order to evaluate the potential impact on the patient compliance of the following categories: age, sex (male vs. female), extent of surgery (pneumectomy vs. lesser resection), stage (I,II vs. III), RT(delivered or not) and patient residence (local vs. remote). RESULTS: One hundred and seventy-nine (50%) patients completed all 6 cycles, while 299 (84%) received at least 4 cycles. The median number of administered cycles was 5. For a target of 4 cycles none of the investigated variables had any significant impact. A significant impact on compliance for 6 cycles was recorded for age (OR 0.97, 95% CI 0.95-0.99, p=0.01) and extent of surgery (OR 0.54, 95% CI 0.33-0.87, p=0.01) CONCLUSION: Using the above mentioned combinations, the patient compliance with adjuvant CT was good, with 84% receiving at least 4 and 50% all 6 cycles. The median number of cycles was 5. For a target of 4 cycles none of the investigated variables had a significant impact. For a longer CT duration, age and extent of surgery were correlated with a lower compliance.

Anthracycline pretreated patients: who is who in the chemotherapy choice of relapsed breast cancer?

During the last years, a strong trend towards excluding anthracyclines from the first-line chemotherapy (CT) of relapsed breast cancer (RBC) has been noticed. This trend is based on the concept of previous exposure of the tumor on the same drugs in the adjuvant setting. Consequently, some guidelines and experts recommend the avoidance of using these compounds for RBC under those circumstances, while the taxanes became the first treatment option. This article gives detailed references about the lack of correlation between the type of adjuvant chemotherapy (including anthracyclines), and the clinical outcome of patients treated with front-line anthracyclines for RBC. It also addresses the weakness of this rationale based on recent translational research data and comments on the fact that anthracyclines could represent the best treatment option for some subcategories of patients with RBC. Concluding, this new trend seems more empirical than evidence-based, and clarification of this issue is warranted.