Friday, February 17, 2012
update FYI: most viewed posts - Ovarian Cancer and Us Blog
Jan 16th - in order of most read/popular (top 5):
this week - in order of most read/popular (top 5):
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Phase II trial of bryostatin-1 in combination with cisplatin in patients with recurrent or persistent epithelial ovarian cancer: a California cancer consortium study.
Phase II trial of bryostatin-1 in combination with cisplatin in patients with recurrent or persistent epithelial ovarian cancer: a California cancer consortium study.
Background
The California Cancer Consortium has performed a Phase II trial of infusional bryostatin, a protein kinase C inhibitor isolated from the marine invertebrate bryozoan, Bugula Neritina, a member of the phylum Ectoprocta, in combination with cisplatin, in patients (pts) with recurrent platinum-sensitive or resistant ovarian cancer (OC).
Methods
Pts received bryostatin 45 mcg/m(2) as a 72 h continuous infusion followed by cisplatin 50 mg/m(2). Cycles were repeated every 3 weeks. Dosages were chosen based on phase I data obtained by the CCC in a population of pts with mixed tumor types.
Results
Eight pts with recurrent or persistent epithelial OC received 23 cycles of treatment. All pts had received previous platinum-based chemotherapy; two pts had received one prior course, five had received two prior courses, and one had received three prior courses of chemotherapy. The median age was 64 (range 32-72), and Karnofsky performance status 90 (range 80-100). A median of 3 cycles of chemotherapy were delivered (range: 1-5). The median progression-free and overall survivals were 3 and 8.2 months respectively. Best responses included two partial responses (one in a platinum-resistant pt), three pts with stable disease, and three progressions. All pts experienced Grade 3 or 4 toxicities including severe myalgias/pain/fatigue/asthenia in six pts, and severe nausea/vomiting/constipation in two other pts. One pt experienced a seizure and liver function tests were elevated in one other.
Conclusions
A modest response rate is observed in pts with recurrent or persistent ovarian cancer treated with the combination of bryostatin and cisplatin. The toxicity profile, however, observed in this pt population (primarily severe myalgias), precludes tolerability and prevents this combination from further investigation at this dose and schedule. It is possible that platinum pre-exposure in OC patients exacerbates observed toxicity. Phase II dosages of investigational agents in OC pts that are determined by phase I trials in pts with other tumor types should be chosen cautiously.
Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors.
Target-specific, histology-independent, randomized discontinuation study of lapatinib in patients with HER2-amplified solid tumors.:
Background:
To explore the activity of lapatinib with a novel trial design focused on the drug target rather than on histology.
Methods:
Patients with HER2 amplified gastro-esophageal, bladder, ovarian, or uterine tumors were enrolled into a double-blinded randomized discontinuation study of lapatinib 1,500 mg PO daily. The planned sample size was 250 patients with HER2 amplified tumors, with the goal of randomizing 100 patients with stable disease (SD) at week 12 to either lapatinib or placebo. Patients responding after 12 weeks continued on lapatinib; those who progressed were discontinued from study. The primary objectives were response rate after 12 weeks and the percentage of patients who remained progression free 12 weeks after randomization to placebo versus lapatinib.
Secondary objectives were duration of response and determination of the incidence of HER2 amplification in multiple tumor types.
Results:
A total of 141 patients were screened and 32 patients with HER2 amplified tumors were enrolled.
At week 12, 1 (3%) patient had a complete response, 9 (28%) had stable disease, 20 (63%) had progressive disease, and 2 (6%) were unknown. Only 7 patients with SD underwent randomization. The low response rate coupled with slow screening and enrollment led to early study closure.
Conclusions:
Basing trial eligibility on the presence of a genetic target, versus histologic classification, is challenging. While HER2 amplifications appear to be prevalent in select non-breast tumors, lapatinib monotherapy is associated with modest activity. The target-specific histology-independent randomized discontinuation design still merits consideration for targets clearly implicated in "oncogene addiction".
abstract: Phase I clinical and pharmacokinetic study of trabectedin and carboplatin in patients with advanced solid tumors (including OC)
Phase I clinical and pharmacokinetic study of trabectedin and carboplatin in patients with advanced solid tumors.
Purpose
This study intended to determine the maximum tolerated dose (MTD) and the recommended phase II dose (RD) of trabectedin combined with carboplatin in patients with advanced solid tumors.
Patients and methods
Carboplatin-pretreated patients received carboplatin AUC 4 (Group 1), whereas carboplatin-naïve patients received carboplatin AUC 5 (Group 2) as a 1-h i.v. infusion followed by trabectedin at dose range from 0.5-1.2 mg/m(2) in the schedule of 3-h/every-3-weeks. Pharmacokinetic (PK) sampling was performed in the first 2 cycles.
Results
Forty-four patients were treated and evaluable for safety and dose-limiting toxicities (DLTs). In Group 1, at trabectedin 1.0 mg/m(2), cumulative hematological toxicity was found in all patients and 1/10 patients had DLTs. The RD was considered trabectedin 0.8 mg/m(2) combined with carboplatin AUC 4. Although no DLT occurred at this dose level, frequent dose delays (28.6%) and the 4-week cycle re-scheduling (66.7%) were required. In Group 2, DLTs occurred at trabectedin 0.8 mg/m(2) (3/8 patients), 1.0 mg/m(2) (3/10 patients) and 1.2 mg/m(2) (2/2 patients) with cumulative hematological toxicity associated with an important number of transfusions. In this group, neither the MTD nor the RD were established. Promising antitumor activity was found for this carboplatin/trabectedin combination; especially in patients with advanced ovarian cancer and soft tissue sarcoma. No significant PK drug-drug interaction occurred.
Conclusions
This study established a trabectedin dose of 0.8 mg/m(2) combined with carboplatin AUC 4 and given every 4 weeks as the most feasible schedule in carboplatin-pretreated patients. Dose and cycle recommendations for carboplatin-naïve patients warrant further evaluation.
Clinical Oncology News - Finding an Avastin (Bevacizumab) Biomarker: An Elusive Target
"On a basic level, it is still somewhat unclear why bevacizumab works on some cancers and not on others because seemingly, all tumors need to be fed by blood vessels."
Still waiting for the world to catch up - Ignace Vergote - Cancer World - including comments on CA-125/biomarkers
"When Ignace Vergote opted to specialise in gynaecological oncology, his country wasn't ready, and he's been waiting for the world to catch up with him ever since....."
~~~~~~~
"....The problem is well illustrated by Vergote’s own experience. When asked
about the research he is most proud of, Vergote points to an academic
study published a year ago in the New England Journal of Medicine,
which was independently funded and has already had a global impact.
Sponsored by the EORTC, it analysed outcomes in advanced ovarian cancer
surgery according to whether the debulking surgery was timed before or
during chemotherapy.
“I was very proud of this. But it took us ten years. We had to randomise
720 patients and, because it wasn’t sponsored, people had to be very
committed and give their time for free – talking to patients, gaining
informed consent, all these things without financial support. It’s very
difficult. So I am proud of that.”...
~~~~~
" He believes that more accurate tumour markers than CA125 need to be found – and his department is working on this problem.
“In 20 years, I think that maybe we will have a marker that will be more
specific and good enough for screening. But I think it’s still too
early to conclude that we have found it.” "
abstract: Preferences for place of death if faced with advanced cancer: a population survey in England, Flanders, Germany, Italy, the Netherlands, Portugal and Spain
Blogger' Note: implications (and distortions) for policy makers continue on this issue aside from this specific paper; assumptions on place of death are generally faulty (IMHO)
~~~~~~~~~~~~~~~
Background: Cancer end-of-life care (EoLC) policies assume people want to die at home. We aimed to examine variations in preferences
for place of death cross-nationally.
Methods: A telephone
survey of a random sample of individuals aged ≥16 in England, Flanders,
Germany, Italy, the Netherlands, Portugal
and Spain. We determined where people would
prefer to die if they had a serious illness such as advanced cancer,
facilitating
circumstances, personal values and experiences
of illness, death and dying.
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