A prospective multicenter (phase IIIb) trialstudy of Treosulfan in elderly patients with recurrent ovarian cancer: results of a planned safety analysis

A prospective multicenter study of treosulfan in elderly patients with recurrent ovarian cancer: results of a planned safety analysis

This open-label multicenter phase-IIIb trial was conducted at 47 German institutions; the first 25 patients analyzed in this safety analysis were recruited in 10 centers.

Background  

Treosulfan, an alkylating agent, has demonstrated activity in recurrent ovarian carcinoma. It is equieffective as oral (p.o.) and intravenous (i.v.) formulation. To explore the preference and compliance of elderly patients regarding p.o. or i.v. treosulfan for the treatment of relapsed ovarian carcinoma, women aged 65 years or older were included in this prospective multicenter study. Since elderly patients usually have several concomitant diseases and experience more treatment toxicity, an interim safety analysis was planned and performed after 25 patients finished therapy to assess the tolerability of the treatment regimens.


Table 1 - 6 

• Patient characteristics
• Concomitant diseases
• Treatment delivery
• Reasons for early therapy discontinuation [less than 12 cycles (i.v.) or 12 months of therapy 
• Non-hematological toxicities: highest grade per patient (in alphabetic order)
• Hematological toxicities: highest grade per patient

"Altogether 16 serious adverse events (SAE) were documented for nine patients. The predominant reason for SAE-reporting was hospitalization (14 reports). Death was the matter for the remaining 2 SAEs. An additional patient was hospitalized due to progressive disease and died in hospital. In all 3 cases, death was concerned as not related to study medication and progress of the underlying malignant tumor was stated as cause of death."

"In summary, the observed toxicities were in the same range as reported in previous studies with significantly younger patients and less comorbidity or with old women having received fewer previous lines of chemotherapy.

There were no unexpected hematological or non-hematological toxicities. Based on this safety analysis, treosulfan proved to be a safe and tolerable therapeutic option in elderly, heavily pretreated patients and the next step of study recruitment was initiated. Of note, the majority of patients in the interim safety population chose i.v. treosulfan over the oral application. Detailed analysis after completion of the trial will hopefully yield new insight into therapy preference and compliance of elderly patients with recurrent ovarian cancer."

Conflict of interest  The trial was supported by Medac GmbH.

Drug data reveal sneaky side effects : Nature News & Comment

Drug data reveal sneaky side effects : Nature 

 Mining of surveillance data highlights thousands of previously unknown consequences when drugs are taken together.

14 March 2012

An algorithm designed by US scientists to trawl through a plethora of drug interactions has yielded thousands of previously unknown side effects caused by taking drugs in combination.
The work, published today in Science Translational Medicine¹, provides a way to sort through the hundreds of thousands of 'adverse events' reported to the US Food and Drug Administration (FDA) each year. “It’s a step in the direction of a complete catalogue of drug–drug interactions,” says the study's lead author, Russ Altman, a bioengineer at Stanford University in California.........“Even if you show a drug is safe in a clinical trial, that doesn’t mean it’s going to be safe in the real world,” says Paul Watkins, director of the Hamner–University of North Carolina Institute for Drug Safety Sciences in Research Triangle Park, North Carolina, who was not involved in the work. “This approach is addressing a better way to rapidly assess a drug’s safety in the real world once it is approved.”.....

A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites

A phase II study of aflibercept in patients with advanced epithelial ovarian cancer and symptomatic malignant ascites

Objective 
The recombinant fusion protein, aflibercept binds and neutralizes vascular endothelial growth factor (VEGF) A, B and placental growth factor (PlGF). Aflibercept inhibits ascites formation and reduces tumor burden in an ovarian cancer model. This open-label, single-arm, multicenter phase II study assessed the efficacy and safety of aflibercept in patients with advanced chemo-resistant epithelial ovarian cancer and symptomatic malignant ascites.

Methods 
Patients who required ≥3 previous paracenteses at 1-4 paracenteses per month received intravenous aflibercept 4mg/kg every 2weeks. The primary endpoint was repeat paracentesis response rate (RPRR), with response defined as at least a two-fold increase in time to repeat paracentesis compared with the baseline interval.

Results 
Ten out of 16 enrolled patients achieved a response; the RPRR was 62.5% (95% CI 35.4%–84.8%). Aflibercept was considered effective based on a hypothesis that the RPRR was ≥60%. Median time to repeat paracentesis was 76.0 (95% CI 64.0–178.0) days, which was 4.5 times longer than the baseline interval (16.8days). Median progression-free survival was 59.5 (95% CI 41.0–83.0) days. Twelve patients experienced adverse events considered related to aflibercept treatment including hypertension (7 patients), headache, anorexia, and dysphonia (3 patients each). Two patients experienced Grade 3/4 treatment-related adverse events (Grade 3 hypertension and weight loss in one patient, Grade 3 intestinal perforation in one patient).

Conclusion 
Aflibercept 4mg/kg every 2weeks was effective at controlling malignant ascites, reducing the interval between repeat paracenteses. The safety profile was consistent with that reported for anti-VEGF agents.

abstract: The clinical effect of the dual-targeting strategy involving PI3K/AKT/mTOR and RAS/MEK/ERK pathways in patients with advanced cancer (phase 1)

Purpose: This study evaluated the clinical relevance of the dual-targeting strategy involving PI3K/AKT/mTOR and RAF/MEK/ERK pathways.

 P

Experimental Design: We investigated safety, efficacy and correlations between tumor genetic alterations and clinical benefit in 236 patients with advanced cancers treated with phase I study drugs targeting PI3K and/or MAPK pathways in our Phase I Clinical Trials Program.

Evidence Updates including professional commentaries - : Acupuncture: does it alleviate pain and are there serious risks? A review of reviews.

Acupuncture is commonly used for pain control, but doubts about its effectiveness and safety remain.

This review was aimed at critically evaluating systematic reviews of acupuncture as a treatment of pain and at summarizing reports of serious adverse effects published since 2000. Literature searches were carried out in 11 databases without language restrictions. Systematic reviews were considered for the evaluation of effectiveness and case series or case reports for summarizing adverse events. Data were extracted according to predefined criteria. Fifty-seven systematic reviews met the inclusion criteria. Four were of excellent methodological quality. Numerous contradictions and caveats emerged. Unanimously positive conclusions from more than one high-quality systematic review existed only for neck pain. Ninety-five cases of severe adverse effects including 5 fatalities were included. Pneumothorax and infections were the most frequently reported adverse effects.

In conclusion, numerous systematic reviews have generated little truly convincing evidence that acupuncture is effective in reducing pain. Serious adverse effects continue to be reported. Numerous reviews have produced little convincing evidence that acupuncture is effective in reducing pain.

Serious adverse events, including deaths, continue to be reported.

full free access: Informa Healthcare -Review Clinical burden of venous thromboembolism

Conclusions:

Even among high-risk groups it is not possible to identify individuals who will go on to develop VTE, and, therefore, thromboprophylaxis is a recommended component of the management of high-risk patients. Ensuring patients receive safe, effective, easily administered antithrombotic therapy both in hospital and post-discharge, for a sufficient length of time, should be central to any strategy to reduce incident or recurrent VTE and minimise the risk of long-term complications.

DMBN Exclusive: Is your MRI suite safe for patients & staff?

Timing of administration of bevacizumab (Avastin) chemotherapy affects wound healing after chest wall port placement - Cancer

Definition: dehiscence - Separation of wound edges.

Abstract
BACKGROUND:

The authors investigated how the timing of administration of bevacizumab, a targeted vascular endothelial growth factor-inhibiting chemotherapeutic agent, affected the risk of wound healing in patients undergoing chest wall port placement.

CONCLUSIONS:

The risk of a wound dehiscence requiring chest wall port explant in patients treated with bevacizumab was inversely proportional to the interval between bevacizumab administration and port placement, with significantly higher risk seen when the interval is less than 14 days.

Safety and tolerability of testosterone patch therapy for up to 4 years in surgically menopausal women receiving oral or transdermal oestrogen - abstr

abstract: Monitoring long-term treatment with pegylated liposomal doxorubicin: how important is intensive cardiac follow-up?

"PLD is cardiac safe for long-term treatment of metastatic solid tumors. Its maximal cumulative dose remains undefined. "

abstract: Expert Opinion on Drug Metabolism & Toxicology - Effects of herbal products on the metabolism and transport of anticancer agents

What the reader will gain: Potential interactions of herbal medicines with anticancer agents have become a safety concern in cancer chemotherapy.

Take home message: Further studies are warranted to investigate the efficacy and safety profiles of herbal medicines commonly used by cancer patients.

FDA to Communicate Safety Monitoring Activities to Consumers and Health Care Professionals

FDA to Communicate Safety Monitoring Activities to Consumers and Health Care Professionals
New website will contain safety reports on recently approved drugs, biologics

Surgical Quality Measures Not Associated with Infection Rates (U.S.)

Safety regulations stalling clinical trials - media article

Preclinical safety data reports Natural S-equol has little effect on 2 reproductive hormones

"About 50 percent of Asians and 20 to 30 percent of North Americans and Europeans, who in general consume less soy than Asians, have the ability to produce equol. Studies in Japan have documented an association between milder menopausal symptoms in equol producers as compared to non-producers."

Phase I Oncology Studies: Evidence That in the Era of Targeted Therapies Patients on Lower Doses Do Not Fare Worse — Dr Maurie Markman et al

abstract:

"Purpose: To safely assess new drugs, cancer patients in initial cohorts of phase I oncology studies receive low drug doses. Doses are successively increased until the maximum tolerated dose (MTD) is determined. Because traditional chemotherapy is often more effective near the MTD, ethical concerns have been raised about administration of low drug doses to phase I patients. However, a substantial portion of oncology trials now investigate targeted agents, which may have different dose-response relationships than cytotoxic chemotherapies.......

abstract: Safety and efficacy results of the advanced renal cell carcinoma Sorafenib expanded access program in North America

Note: while this is not specific to ovarian cancer knowing the side effects which patients experienced may be helpful

Doctor and Patient - Holding Doctors Accountable for Medical Errors - NYTimes.com

Editorial Comment: The emphasis of this article seems to place a rather large burden on physicians which is not totally warranted.

Doctor and Patient - Holding Doctors Accountable for Medical Errors - NYTimes.com

Q. What is a major patient safety area that still needs to be addressed?
A. Ten years ago, we approached patient safety as a series of system flaws; we believed that most errors were committed by good competent people doing something no more complicated than forgetting a cellphone. But in the last few years some of us in the patient safety field have begun to feel uneasy about that approach. When there are reasonably safe standards available, what do you do when people simply don’t adhere to them? At some point, it’s no longer a “systems problem.”