open access: BRCA1 is an essential regulator of heart function and survival following myocardial infarction (in research, references doxorubicin)

Blogger's Note: technical paper, in research (eg. mice, tissue samples)

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BRCA1 is an essential regulator of heart function and survival following myocardial infarction

"BRCA1 mutation carriers, in addition to risk of breast and ovarian cancer, may be at a previously unrecognized risk of cardiac failure."

Medpage SGO news: :Combo Promising for Resistant Ovarian Cancer - in Meeting Coverage, SGO from MedPage Today

Medical News:Combo Promising for Resistant Ovarian Cancer - in Meeting Coverage, SGO from MedPage Today

"....The between-group difference increased to 4 months in the subgroup of patients whose lesions had imaging-confirmed folate-receptor expression.
Overall survival did not differ between the groups, due in part to an unusually prolonged survival in the control arm, R. Wendel Naumann, MD, said here at the Society of Gynecologic Oncology meeting.
"This is the first clinical trial that has shown a benefit in progression-free survival over standardized therapy in a randomized trial in patients with platinum-resistant ovarian cancer, and we think it's pretty exciting," said Naumann, of Carolinas Medical Center in Charlotte, N.C.
"We know that EC20 scanning identifies patients who will benefit most from the combination of pegylated liposomal doxorubicin and vintafolide, as well as those who will not benefit. It appears that patients in whom all lesions are folate-receptor positive benefit the most from this combination."
A phase III randomized trial of PLD plus vintafolide has already begun, he added.............

Action Points

• This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Note that a compound which binds with high affinity to the folate receptor, which is expressed on the majority of epithelial ovarian cancers, and releases a cytotoxic component significantly increased progression-free survival in this phase two study.

abstract: Vinblastine, cisplatin, cyclophosphamide, bleomycin, doxorubicin, and etoposide (VPCBAE) in the management of three patients with small-cell carcinoma of the ovary

Vinblastine, cisplatin, cyclophosphamide, bleomycin, doxorubicin, and etoposide (VPCBAE) in the management of three patients with small-cell carcinoma of the ovary: Publication year: 2012
Source: Gynecologic Oncology Case Reports, Available online 13 February 2012
abstract

Highlights

► Ovarian small-cell carcinoma of the hypercalcemic type is a rare neoplasm with no standard treatment.
► The chemotherapy regimen including vinblastine, cisplatin, cyclophosphamide, bleomycin, doxorubicin and etoposide (VPCBAE) is safe and effective.has limited toxicities and was effective in the 3 patients described in this case report.

abstract: Pegylated liposomal doxorubicin: appraisal of its current role in the management of epithelial ovarian cancer.

Markman M.

Source

Cancer Treatment Centers of America, Eastern Regional Medical Center, Philadelphia, PA, USA.

Abstract

Pegylated liposomal doxorubicin (PLD) has become a major component in the routine management of epithelial ovarian cancer. The drug is frequently employed as a single agent in the platinum-resistant setting, and recently reported data reveal the superiority of the combination of PLD plus carboplatin, compared with the platinum drug plus paclitaxel, in delaying the time to disease progression in women with recurrent (potentially platinum-sensitive) disease. Current research efforts involving PLD in ovarian cancer are focusing on adding novel targeted drugs to this cytotoxic agent. The utility of such approaches in the platinum-resistant population, compared with the sequential administration of single agents active in this setting, remains to be determined.

Long-Term Doxorubicin Linked to Secondary Oral Cancers

".......Four patients who received long-term PLD for advanced-stage ovarian cancer developed malignant and/or premalignant lesions of the tongue and/or oral cavity. Dr. Cannon points out that there were only about 16 patients who received PLD for an extended period of time, "so 4 out of 16 patients is quite high."
All 4 of the patients had received maintenance therapy with PLD for at least 3 years. Of this group, 3 women were subsequently diagnosed with squamous cell carcinoma (SCC) of the tongue and/or oral cavity, and 1 patient was diagnosed with sublingual mucosa high-grade dysplasia. All 3 cases of SCCs were negative for human papillomavirus.

Of note, said Dr. Cannon, was a patient who presented with 3 separate lesions of SCC of the oral cavity.

"I don't think this is a coincidence, that 4 of 16 patients receiving this treatment developed oral cancers," he said. "If this treatment for ovarian cancer becomes more popular, then this is something that should become known. Early dental screening would need to be initiated, and the treatment may need to be stopped after a certain time period."

It is relatively uncommon for ovarian cancer patients to receive PLD for this length of time.......cont'd

also: see chart

Clinical consequences of the Calypso trial showing superiority of PEG-liposomal doxorubicin and carboplatin over paclitaxel and carboplatin in recurrent ovarian cancer: Results of an Austrian gynecologic oncologists' expert meeting.

A double-blind, randomized trial of pyridoxine versus placebo for the prevention of pegylated liposomal doxorubicin-related hand-foot syndrome in gyne

Blogger's Note: in the absence of full access to the article, this conclusion 'needs more research'


"CONCLUSIONS:: Pyridoxine as administered in the current study did not prevent HFS in patients who received PLD. It is possible that QOL is not compromised in patients with HFS because they may have increased social well being while coping with their disease."

repost: abstract: (Yondelis) Trabectedin Plus Pegylated Liposomal Doxorubicin in Recurrent Ovarian Cancer. BJ Monk et al

Note: Reposted from June 9th to coincide with Editorial from JCO; multinational study plus: JCO link

Pegylated Liposomal Doxorubicin and Carboplatin Compared With Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian Cancer in Late Relapse

Pegylated Liposomal Doxorubicin and Carboplatin Compared With Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian Cancer in Late Relapse  
ABSTRACT  

Purpose This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of the combination of pegylated liposomal doxorubicin (PLD) with carboplatin (CD) compared with standard carboplatin and paclitaxel (CP) in patients with platinum-sensitive relapsed/recurrent ovarian cancer (ROC).  

Patients and Methods Patients with histologically proven ovarian cancer with recurrence more than 6 months after first- or second-line platinum and taxane-based therapies were randomly assigned by stratified blocks to CD (carboplatin area under the curve [AUC] 5 plus PLD 30 mg/m2) every 4 weeks or CP (carboplatin AUC 5 plus paclitaxel 175 mg/m2) every 3 weeks for at least 6 cycles. Primary end point was progression-free survival (PFS); secondary end points were toxicity, quality of life, and overall survival.  

Results Overall 976 patients were recruited. With median follow-up of 22 months, PFS for the CD arm was statistically superior to the CP arm (hazard ratio, 0.821; 95% CI, 0.72 to 0.94; P = .005); median PFS was 11.3 versus 9.4 months, respectively. Although overall survival data are immature for final analysis, we report here a total of 334 deaths. Overall severe nonhematologic toxicity (36.8% v 28.4%; P < .01) leading to early discontinuation (15% v 6%; P < .001) occurred more frequently in the CP arm. More frequent grade 2 or greater alopecia (83.6% v 7%), hypersensitivity reactions (18.8% v 5.6%), and sensory neuropathy (26.9% v 4.9%) were observed in the CP arm; more hand-foot syndrome (grade 2 to 3, 12.0% v 2.2%), nausea (35.2% v 24.2%), and mucositis (grade 2-3, 13.9% v 7%) in the CD arm.  

Conclusion To our knowledge, this trial is the largest in recurrent ovarian cancer and has demonstrated superiority in PFS and better therapeutic index of CD over standard CP.

Different anthracycline derivates for reducing cardiotoxicity in cancer patients. Cochrane Collaboration Database Systematic Review

CONCLUSIONS:
We are not able to favour either epirubicin or doxorubicin when given with the same dose. Based on the currently available evidence on heart failure, we conclude that in adults with a solid tumour liposomal-encapsulated doxorubicin should be favoured over doxorubicin. For both epirubicin versus doxorubicin and liposomal-encapsulated doxorubicin versus conventional doxorubicin no conclusions can be made about the effects of treatment in children treated with anthracyclines and also not in patients diagnosed with leukaemia. More research is needed. For other combinations of anthracycline derivates not enough evidence was available to make definitive conclusions about the occurrence of cardiotoxicity in patients treated with anthracyclines.

CCardiology

Probably an important review but it would have been more helpful for the general practitioner if the authors also reviewed or at least discussed the role of ACE-Inhibitors given before anthracycline treatment in these patients.

ommentary (1) at present:

Phase I trial of ixabepilone plus pegylated liposomal doxorubicin in patients with adenocarcinoma of breast or ovary

Abstract  
Background: Ixabepilone is a semisynthetic epothilone B analogue that is active in taxane-resistant cell lines and has shown activity in patients with refractory breast and ovarian cancer. We carried out a phase I trial of ixabepilone plus pegylated liposomal doxorubicin (PLD) in patients with advanced taxane-pretreated ovarian and breast cancer.