martes, 1 de noviembre de 2011

Pemetrexed single agent for "continuation maintenance" therapy in patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC)

October 28, 2011 — The European Commission has approved pemetrexed (Alimta, Eli Lilly) for use as a single agent for "continuation maintenance" therapy in patients with advanced nonsquamous nonsmall-cell lung cancer (NSCLC), the company announced today. Pemetrexed is the first chemotherapy agent to be approved in Europe for continuation maintenance therapy, according to Eli Lilly. Continuation maintenance therapy refers to the first-line use of a therapy and then its ongoing use in nonprogressors. Other maintenance regimens are currently available for NSCLC, according to a company press statement, but they involve "switch maintenance," in which nonprogressing patients are switched from their first-line treatment to another drug during the maintenance phase. Continuation maintenance therapy is not for every NSCLC patient who responds to first-line treatment, according to a pemetrexed investigator. "Some may have significant toxicity during induction treatment, and it may be worth having a treatment break. [However], a patient who is having a good response in the absence of significant toxicity may be a good candidate for maintenance therapy," said Luis Paz-Ares, MD, PhD, from the Seville University Hospital in Spain, in a press statement at the 2011 annual meeting of the American Society of Clinical Oncology (ASCO). Dr. Paz-Ares was the lead author of the study on which the European approval is based. That phase 3 study, known as PARAMOUNT, is the first large trial to demonstrate that using continuation maintenance therapy can increase progression-free survival in this setting. The study results were first presented at the 2011 ASCO meeting, and were reported by Medscape Medical News at that time. In an earlier study, pemetrexed was found to increase progression-free survival and overall survival, compared with placebo, in this same patient population when used in switch maintenance. In PARAMOUNT, 939 patients were given the standard 4 courses of first-line induction treatment with pemetrexed and cisplatin to induce disease remission. Nonprogressors with a good performance status were then randomized (in a 2:1 ratio) to either maintenance pemetrexed (n = 359) or placebo (n = 180). Median progression-free survival was 4.1 months in the pemetrexed group and 2.8 months in the placebo group. Continuation maintenance therapy with pemetrexed resulted in a significant 38% reduction in the risk for disease progression (hazard ratio, 0.62; P = .00006). Pemetrexed is approved in Europe and the United States for 3 indications in patients with advanced nonsquamous NSCLC — first-line treatment in combination with cisplatin, second-line treatment, and maintenance treatment for patients whose disease does not progress immediately after platinum-based chemotherapy. Maintenance therapy is a controversial treatment strategy in lung cancer and has been discouraged in certain patients by various experts.

domingo, 10 de julio de 2011

Cuando estoy triste entiendo las estupideces que hago en la vida...

Foto David Muñoz Carmona© Si usas la foto comenta la fuente

Three-dimensional conformal radiation therapy for non–small-cell lung cancer: A Phase I/II dose escalation clinical trial☆

Three-dimensional conformal radiation therapy for non–small-cell lung cancer: A Phase I/II dose escalation clinical trial☆
Kai-Liang Wu, M.D., Guo-Liang Jiang, M.D., Yuan Liao, Ph.D., Hao Qian, M.D., Li-Juan Wang, M.D., Xiao-Long Fu, M.D., Shen Zhao, M.D.

A prospective Phase I/II dose escalation study was conducted to determine the maximum tolerated dose (MTD) in three-dimensional conformal radiation therapy (3D-CRT) for non–small-cell lung cancer (NSCLC).

Methods and materials
MTD would be reached via a dose escalation study. After 42 Gy/21 fractions, 4.2 weeks by conventional fractionated irradiation through anteroposterior/posteroanterior fields, the 3D-CRT technique was used as boost. The planned total dose escalation depended on lung volume irradiated. According to the percentage of lung volume receiving >20 Gy, the patients were divided into three subgroups (i.e., <25%, 25%–37%, and >37%). The scheduled dose escalation began with 69 Gy and continued to 78 Gy. The boost doses were delivered at 3 Gy per fraction, once per day, five fractions per week. Each dose level includes 5 patients. Besides radiotherapy, all patients received neoadjuvant and adjuvant chemotherapy with MVP regimen (Mitomycin, Vindesine, cis-platium). The criterion for stopping further dose escalation was ≥20% of patients with ≥RTOG Grade 3 radiation pneumonitis.

Between June 1999 and February 2001, 50 patients had been enrolled in this study, including 4 with Stage II disease, 31 with Stage IIIa disease, and 15 with Stage IIIb disease. The dose escalation plan has been completed. All subgroups reached the highest predetermined dose levels (i.e., 78 Gy for the <25% subgroup, 78 Gy for the 25–37% subgroup, and 75 Gy for the >37% subgroup). Although none of the subgroups developed more than 20% of ≥Grade 3 acute pneumonitis, dose escalation was terminated because long-term follow-up was needed to observe late complications. Median follow-up time (MFT) for the entire group was 18 months (6–37 months). The most common acute complication was esophagitis in 56% of patients with RTOG Grade 1–2, and in 4% with Grade 3. Acute radiation pneumonitis developed in 36% of patients with RTOG Grade 1–2. Only 1 patient had Grade 3 pneumonitis, which was in the 25–37% subgroup at 75 Gy. The hematopoietic toxicity appeared in 58% of patients with Grade 1–2, and 8% with Grade 3. As to late complications, only 30% of patients developed pulmonary fibrosis of RTOG Grade 1–2. The median survival time for the entire group was 18 months. Two-year overall survival, locoregional progression-free rate, and distant metastasis rate were 44%, 40%, and 41%, respectively.

Although MFT was 18 months, it had not yet been declared because a longer follow-up was needed to observe the late complications. The 2-year overall survival of 44% was very encouraging and implied that 3D-CRT combined with chemotherapy would improve the outcome for locally advanced NSCLC.

CRUK/07/001: QUARTZ - A phase III multicentre randomised trial to assess dexamethasone +/- whole brain radiotherapy in patients with inoperable brain

Paula Mulvenna
Medical Research Council
01 January 2007 to 31 December 2013
Clinical Trials Awards & Advisory Committee - Late Phase Study
Funding committee - Clinical Trials Awards and Advisory Committe

Cerebral metastases, from any primary, are a devastating occurrence and most patients deteriorate quickly over a matter of weeks. A number of treatment options have been investigated, but for many years, the standard therapy for patients with inoperable brain metastases has remained a combination of steroids and Whole Brain Radiotherapy (WBRT). However, WBRT can be toxic and has not been shown to consistently improve length or quality of survival, particularly for patients with a non-small cell lung cancer primary.
The aim of this trial is to determine whether dexamethasone alone is as effective as dexamethasone plus WBRT in terms of overall quality of survival time for patients with inoperable brain metastases originating from non-small cell lung cancer, when both groups of patients are also receiving optimal supportive care At the time of referral to the oncology centre, the vast majority of patients will be receiving optimal supportive care (OSC) including dexamethasone for symptom relief. Patients will continue to receive this treatment and in addition will be allocated WBRT (20 Gy in 5 consecutive daily fractions) or not. Because these patients have a short survival time, and may not be well enough to be seen in clinic; a nurse will assess all patients via a weekly telephone call.

sábado, 16 de abril de 2011

ASCO, NCCN Recommend EGFR Testing in Advanced Lung Cancer

Testing for epidermal growth factor receptor mutations is an important step in the evaluation process for systemic therapy in patients with metastatic or recurrent non-small cell lung cancer according to updated recommendations issued by the American Society of Clinical Oncology and the National Comprehensive Cancer Network.

ASCO issued a provisional clinical opinion (PCO) on April 7 that patients with advanced non-small cell lung cancer (NSCLC) who are being considered for treatment with one of the tyrosine kinase inhibitors (TKIs) that target the epidermal growth factor receptor (EGFR) should undergo EGFR-mutation testing.

Oncologists have learned that NSCLC is "really a collection of genetically distinct diseases," ASCO's PCO panel cochair Dr. Vicki L. Keedy of Vanderbilt-Ingram Cancer Center in Nashville, Tenn., said in a press release. The goal is to "treat patients with drugs that target the molecular drivers of their specific tumors rather than using a one-size-fits-all approach."

The NCCN earlier updated its clinical management guidelines to include a category 1 recommendation that EGFR testing should be undertaken after histologic diagnosis of adenocarcinoma, large cell carcinoma, or undifferentiated carcinoma.

The NCCN recommendation does not extend to patients with squamous cell lung cancer, because the incidence of EGFR mutation in this patient subgroup is less than 3.6%, Dr. David S. Ettinger said in March at the organization's annual conference.

Both groups based their endorsements on studies demonstrating that mutations in two regions of EGFR gene appear to predict tumor response to chemotherapy in general, and to TKIs specifically.

Among the research priorities that were identified by ASCO, Dr. Keedy noted the trials that are designed to discern whether first-line treatment with a TKI in EGFR mutation-negative patients delays chemotherapy or affects outcome; whether chemotherapy prior to TKI treatment in EGFR mutation-positive patients affects outcome; and whether there are clinically significant differences between erlotinib (Tarceva) and gefitinib (Iressa) among EGFR mutation-positive patients.

The last question is of particular interest, because gefitinib is not Food and Drug Administration approved outside a special program in the United States, whereas erlotinib is currently approved as second-line therapy, she said.

Dr. Ettinger, chair of the NCCN's NSCLC guideline panel and professor of oncology at Johns Hopkins University in Baltimore, cited findings from the landmark IPASS (Iressa Pan-Asia Study) investigation that compared progression-free and overall survival in 1,217 East Asian patients with advanced NSCLC that was treated with the gefitinib or standard carboplatin and paclitaxel chemotherapy.

IPASS demonstrated that EGFR mutation strongly predicted a lower risk of progression on gefitinib vs. chemotherapy (hazard ratio, 0.48), whereas wild-type EGFR predicted a higher risk of progression on gefitinib relative to chemotherapy (HR, 2.85) (N. Engl. J. Med. 2009;361:947-57).

Similarly, in a pooled analysis of clinical outcomes of NSCLC patients who were treated with erlotinib, EGFR mutations were associated with a median progression-free survival of 13.2 vs. 5.9 months (J. Cell. Mol. Med. 2010;14:51-69). Neither study demonstrated a difference in overall survival among treated patients with and without EGFR mutations, Dr. Ettinger said.

The updated NCCN guidelines also state that the sequencing of KRAS (a G protein involved in the EGFR-related signal transmission) could be useful for the selection of patients as candidates for TKI therapy. The KRAS gene can harbor oncogenic mutations that may render a tumor resistant to EGFR-targeting agents, Dr. Ettinger explained, noting that studies have shown that a KRAS mutation in patients with NSCLC "confers a high level of resistance" to TKIs.

Although the data - which primarily come from retrospective reviews with small sample sizes - are insufficient to make a determination about an association between KRAS mutation status and survival, he said, they are sufficient to warrant a category 2A recommendation for sequencing, as well as a recommendation that patients with a known KRAS mutation should undergo first-line therapy with an agent other than a TKI.

Individuals who test negative for EGFR and KRAS should also be screened for a mutation of the anaplastic lymphoma kinase (ALK) fusion gene, Dr. Ettinger said. "Patients who screen positive may not benefit from EGFR TKIs, but they may be good candidates for an ALK-targeted therapy," he said, noting that the investigational ALK-targeting drug crizotinib, in particular, has demonstrated positive results in early studies of NSCLC patients with echinoderm microtubule-associated proteinlike 4 (EML4)-ALK translocations (N. Engl. J. Med. 2010;363:1693-703).

With respect to first-line systemic therapy, patients with adenocarcinoma, large cell carcinoma, or NSCLC "not otherwise specified" who have an Eastern Cooperative Oncology Group/World Health Organization performance status grade of 0-4 and who test positive for the EGFR mutation prior to first-line therapy should be treated with erlotinib, according to the NCCN guidelines. Alternatively, the guidelines state that gefitinib can be used in place of erlotinib "in areas of the world where it is available."

For patients in whom the EGFR mutation is discovered during chemotherapy, the guidelines recommend either adding erlotinib to the current chemotherapy protocol or switching to erlotinib as maintenance treatment."

For patients whose EGFR status is negative or unknown, even in the presence of clinical characteristics that might be suggestive of a mutation (for example, female, nonsmoker, Asian race), conventional chemotherapy is recommended, Dr. Ettinger said.

The updated NCCN guidelines for NSCLC are posted at

The guidelines take a conservative stance on the National Lung Screening Trial finding that screening with low-dose helical CT was associated with a 20% reduction in lung cancer deaths vs. screening with standard chest x-ray. Despite this positive finding, "the NCCN panel does not recommend the routine use of screening CT as a standard clinical practice," said Dr. Ettinger; more conclusive data from ongoing national trials are needed to define the associated risks and benefits. "High-risk patients should participate in a clinical trial evaluating CT screening or go to a center of excellence to discuss the potential risks and benefits of a screening CT," Dr. Ettinger said.

Other notable updates include the following:

• The addition of EBUS (endobronchial ultrasound) as a work-up recommendation.

• The recommendation that bevacizumab (Avastin) and chemotherapy or chemotherapy alone is indicated in performance status 0-1 patients with advanced or recurrent NSCLC, and that bevacizumab should be given until disease progression.

• The recommendation against systemic chemotherapy in performance status 3-4 NSCLC patients.

• The guidance that chemoradiation is better than chemotherapy alone in locally advanced NSCLC, and that concurrent chemoradiation is better than sequential chemoradiation.

• The addition of denosumab (Xgeva) as a treatment option for patients with bone metastases.

• The recommendation favoring cisplatin/pemetrexed (Alimta) vs. cisplatin/gemcitabine (Gemzar) in patients with nonsquamous histology.

• The recommendation against adding a third cytotoxic drug, with the exception of bevacizumab or cetuximab (Erbitux), in treatment-naive performance status 0-1 NSCLC patients.

• The guidance that cisplatin-based combinations are better than best supportive care in advanced, incurable disease, with improvement in median survival and 1-year survival rates.

miércoles, 16 de febrero de 2011

Postoperative radiotherapy and concomitant temozolomide for elderly patients with glioblastoma

Radiotherapy & Oncology
Volume 97, Issue 3 , Pages 382-386, December 2010
Johanna Gerstein, Kea Franz, Joachim P. Steinbach, Valker Seifert, Inge Fraunholz, Christian Weiss, Claus Rödel

The addition of temozolomide (TMZ) to radiotherapy (RT) improves survival of patients with glioblastoma (GB) when compared to postoperative RT alone in patients up to 65years of age. In older patients, RT alone has remained the standard of care because there is concern that radiochemotherapy causes excess toxicity and is less efficacious in this population, but no randomized trials have been reported. We retrospectively assessed feasibility, toxicity and outcome in elderly patients treated at a single institution with RT and concomitant TMZ.
Patient and methods
Between 04/1999 and 9/2009, 51 patients65years (median age 70years, range 65–84) with GB were treated by RT (total dose 60Gy in 30 fractions) and concomitant TMZ (75mg/m2/day throughout RT). Biopsy only had been performed in 23 patients (45.1%), 15 patients (29.4%) had undergone partial resection, and 13 patients (25.5%) macroscopically complete resection. Adjuvant TMZ was applied in 10 of 51 patients.
Median overall survival (OS) and progression-free survival (PFS) were 11.5 (95% CI, 6.7–16.3) and 5.5months (95% CI, 3.7–7.3months), respectively, in the total cohort. After complete resection, partial resection and biopsy, median OS was 27.4, 15.5 and 7.9months (p=0.002), respectively. In multivariate Cox proportional hazards regression models extent of resection (p<0.0001) and Karnofsky’s performance score (p=0.002) were significant independent prognostic factors for OS. RT with concomitant TMZ was well tolerated in the majority of patients and could be completed as scheduled in 30 patients (59%). Five patients (10%) discontinued RT because of disease progression (n=4) or toxicity (pneumonia, n=1). Another 16 patients interrupted concomitant chemotherapy (cytopenia: 9; pneumonia: 2; transaminase elevation: 2; rash: 3).
RT with concomitant TMZ is a feasible regimen with acceptable toxicity in elderly patients. The promising outcome in patients with good performance status and patients with gross total resections are notable.
Keywords: Glioblastoma, Radiotherapy and concomitant temozolomide, Elderly patients

domingo, 6 de febrero de 2011

Berlin The Wall....Bien merece un comentario de todos...

Si quereis comentar algo, esta imagen está para que nos trasmitáis vuestra impresión.

¿Qué queda de la represión...?

¿Todavía pensamos en ella...?

¿Seguimos anclados en el pasado....?

¿Qué necesitamos para el futuro...?

¿Qué os gustaría cambiar de vuestra vidas...?

¿muchas cosas o pocas...?

...Sed valientes, algunos no lo somos lo suficiente, podeis escribir lo que penseis.

Ah, la foto es de David Muñoz Carmona, con una cámara algo mala, pero ¿a que es bonita....?
Saludos a todos desde el otro lado de la montaña