Monotherapy Docetaxel Research Articles

Nivolumab in second-line treatment of squamous non-small cell lung cancer.

The treatment of non-small cell lung cancer (NSCLC) is changing dramatically in the last period, considering both non-squamous and squamous disease. In the last five years, the identification of different molecular predictive biomarker (e.g., EGFR, ALK e ROS1) and the utilize of new chemotherapy agents associated or not with antiangiogenics agents (e.g., bevacizumab and nintedanib), allowed the improvement of survival and related responses to these treatments. However, these advances, did not allow an improvement of the same endpoints in the management of NSCLC with squamous cell histology (SCC), where until very recently, docetaxel in monotherapy remained as a corner stone treatment for the second line, although associated with an unfavorable toxicity profile. In recent years, the improvement knowledge of mechanisms of immune response in patients suffering from solid tumors, and especially lung cancer, allowed the identification of different anti-PD1 and anti-PDL1 monoclonal antibodies (e.g., atezolizumab, avelumab, nivolumab, pembrolizumab) able to improved survival and response when used in second-line setting. In this review, we report the evidences of nivolumab in NSCLC with squamous histology, through the discussion of data related to phase I, II and III published and searchable via Medline/PubMed.

Actualités dans le cancer de la prostate lors de l'Asco 2010

In urologic oncology, prostate cancer represented, even this year, a wide part during the ASCO 2010 meeting. In the non metastatic diseases, two phase III trials confirmed the benefit of radiotherapy combined with hormonotherapy in locally advanced stage. For patients with metastatic hormonoresistant cancer, two randomized trials will probably change the daily practice in the next months. On the one hand, denosumab versus zoledronate decreased significantly the risk of skeletal-related events in bone metastases. On the other hand, compared with mitoxantrone, cabazitaxel in docetaxel pretreated patients improved overall survival. On the contrary, docetaxel in monotherapy remains the standard of care in first line chemotherapy in castration refractory metastatic prostate cancer. Indeed, in two trials, combination of bevacizumab or calcitriol with docetaxel showed no benefit for patients with more toxicities. Finally, docetaxel-based chemotherapy was again evaluated in two other situations: biological recurrence, and hormono-sensitive metastatic stage. Preliminary results of tolerance were presented this year. No doubt that communications during future ASCO meetings would reported definitive results of efficiency of these phase III studies.

Combined effect of sodium selenite and docetaxel on PC3 metastatic prostate cancer cell line

Docetaxel and sodium selenite are well known for their anticancer properties. While resistance to docetaxel remains an obstacle in prostate cancer chemotherapy, sodium selenite, has been exploited as a new therapeutic approach. Currently, development of therapies affecting a multitude of cell targets, have been proposed as a strategy to overcome drug resistance. This association may reduce systemic toxicity counteracting a wide range of side effects.Here we report the effect of docetaxel and sodium selenite combination on the PC3 prostate cancer cell line, derived from bone metastasis. Therefore we evaluate cell growth, cell cycle progression, viability, mitochondria membrane potential, cytochrome C, Bax/Bcl2 ratio, caspase-3 expression and reactive oxygen species production.Our results suggest that sodium selenite and docetaxel combination have a synergistic effect on cell growth inhibition (67%) compared with docetaxel (22%) and sodium selenite (24%) alone. This combination also significantly induced cell death, mainly by late apoptosis vs necrosis, which is correlated with mitochondria membrane potential depletion. On the other hand, cytochrome C, Bax/Bcl2 ratio and caspase-3, known as proapoptotic factors, significantly increased in the presence of sodium selenite alone, but not in the presence of docetaxel in monotherapy or in combination with sodium selenite.These findings suggest that docetaxel and sodium selenite combination may be more effective on prostate cancer treatment than docetaxel alone warranting further evaluation of this combination in prostate cancer therapeutic approach.

A simultaneous analysis of the time-course of leukocytes and neutrophils following docetaxel administration using a semi-mechanistic myelosuppression model

To improve the predictive capacity of a semi-mechanistic myelosuppression model for neutrophils as the model have shown to over-predict the nadir of neutrophils and, secondly, to develop a model describing the time-course of leukocytes and neutrophils simultaneously. The study included 601 cancer patients treated with a 1 h infusion of docetaxel in monotherapy. A total of 3,549 pairwise observations of leukocytes and neutrophils from one treatment cycle were analyzed simultaneously in NONMEM. A basic model was developed consisting of a neutrophil and a non-neutrophil model, each with the same structure as the semi-mechanistic myelosuppression model. The leukocytes were modeled as the sum of the predicted neutrophils and non-neutrophils. The model described the time-course of the leukocytes well, but was not able to capture the nadir of the neutrophils. Hence the model was further refined and the included modifications (p < 0.001) in the final model are a sigmoid Emax functions for the drug effect, feedback functions on the cell maturation time in bone-marrow and an optimized number of transit compartments for each of the two cell types. A joint semi-mechanistic myelosuppression model describing the time-course of leukocytes and neutrophils following docetaxel administration was developed. The data supported a more complex model compared to the previous model developed by Friberg et al. (2002), and increased the model's capacity to accurately describe the time-course of neutrophils following docetaxel therapy. The combined model also illustrates the differences between the cell types and allows prediction of neutrophil counts from leukocyte measurements.

Pemetrexed na segunda linha de tratamento do carcinoma do pulmão de não pequenas células – A experiência portuguesa

Until 2004, docetaxel in monotherapy was the standard for second-line treatment of non-small cell lung cancer (NSCLC). Pemetrexed (P) has shown similar activity in this setting with a better adverse event profile. In Portugal, it was introduced in October of 2004.We have carried out a retrospective analysis of patients (pts) who received P for second-line NSCLC in Portugal from October 2004 to December 2006. Data were collected from the records of pts with locally advanced or metastatic NSCLC and failed first-line chemotherapy enrolled in centers participating in the Portuguese Lung Cancer Study Group (GECP). Objective response (OR; complete [CR] or partial [PR] response) was evaluated using RECIST and safety was assessed using serious or non-serious adverse events (SAEs/AEs).By December 2006, 19 GECP centers had enrolled 244 pts who had received P for ≥1cycle, and were considered evaluable for both objective response and safety. Demography: male/female, 175/69; median age, 57.0years (range 20-81); smoking status, y/ex/n, 116/57/71; adenocarcinoma / squamous-cell carcinoma/other histology, 141/72/31; mean time to progression (TTP) 8.07months. Disease control in 209 evaluable pts was observed in 116 (55.5%): 2 CR, 45 PR and 69 SD; mean TTP 4.70months. The majority of AEs were grade 3 anemia (15 pts) and neutropenia (18 pts). The mean overall survival was 17.27months.Our retrospective analysis has observed a similar disease control rate with P in 2nd line (55.5%), and TTP (4.7months) in our current unselected population to that published in the literature. P is an option for second-line NSCLC with a good tolerability.Rev Port Pneumol 2008; XIV (Sup.2): S9-S20

Randomized study comparing efficacy/toxicity of monotherapy trastuzumab followed by monotherapy docetaxel at progression, and combination trastuzumab/docetaxel as first-line chemotherapy in HER2-neu positive, metastatic breast cancer (MBC) (HERTAX study)

1014 Background: Treatment with trastuzumab and chemotherapy has improved the outcome of HER2-positive MBC. It is unknown what the outcome and toxicity is of monotherapy trastuzumab, followed by chemotherapy at progression, as compared to the combination of chemotherapy/trastuzumab. Methods: HER2-positive MBC pts., being eligible for first line chemotherapy were randomised between combination treatment docetaxel (TAX) (100 mg/m2, q3wks)/trastuzumab (HER) (loading dose 4mg/kg, whereafter weekly 2mg/kg) (arm A) or monotherapy HER, followed upon progression by TAX (similar doses as arm A) (arm B). Further in- /exclusion criteria were adjuvant non-taxoid chemotherapy allowed, previous HER treatment not; normal ejection fraction (EF), adequate liver/renal functions and bone marrow reserve. Primary endpoint was PFS, secondary endpoints: response rate (RR), overall survival (OS) and toxicities. Kaplan-Meier curve was tested by log-rank test, RR by Pearson χ2-test. Results: Of the 101 randomly selected patients, 2 were ineligible. Patient characteristics in arms A/B were not significantly (NS) different, being: median age 52/53 yrs (range 32–74); ER/PgR positive 47/47%; adjuvant chemo-/hormone therapy in 46/25% and 42/33%, respectively; prior hormone therapy for MBC in 37/36%. Objective RRs were 57% and 34% (p=0.03). PFS in arm A was 9.1 mo, while PFS on HER was 3.9 mo (p=0.0001), and after consecutive TAX 9.8 mo (arm B) (p=0.22). OS data is being analysed, and will be presented. Grade 3/4 neurosensory toxicity was only seen in arm A (6%). Other grade 3/4 toxicity was NS different (pulmonary complaints (9%), fatigue (8%), other ≤5%). Serious adverse events more frequently occurred in arm A (25/4), 2 toxic deaths in arm A, neutropenic fever 27/16%. LVEF decline >20% occurred in 16/15%. Conclusions: Monotherapy HER followed by monotherapy TAX yields a similar PFS as compared to combination therapy HER/TAX, and is associated with less grade 3/4 toxicity. Cardiac toxicity is NS different between both treatment modalities. Delaying cytotoxic therapy by using monotherapy HER may be a treatment option for particular patients. No significant financial relationships to disclose.

PCN36 A COST UTILITY ANALYSIS OF FIRST-LINE CHEMOTHERAPY REGIMENS IN THE TREATMENT OF METASTATIC BREAST CANCERAFTERANTHRACYCLINE FAILURE

OBJECTIVES : Four chemotherapy regimens: gemcitabine-paclitaxel (Gem/Pac), paclitaxel in monotherapy (Pac), docetaxel in monotherapy (Doc) and docetaxel-capecitabine in association (Doc/Cap), are commonly used in the first-line treatment of metastatic breast cancer after anthracyclines failure. The purpose of the study is to rank these strategies according to their incremental cost-utility ratios.