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.
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.
Authors: D S Alberts; P Y Liu; E V Hannigan; R O'Toole; S D Williams; J A Young; E W Franklin; D L Clarke-Pearson; V K Malviya; B DuBeshter Journal: N Engl J Med Date: 1996-12-26 Impact factor: 91.245
Authors: M L Varterasian; R M Mohammad; D S Eilender; K Hulburd; D H Rodriguez; P A Pemberton; J M Pluda; M D Dan; G R Pettit; B D Chen; A M Al-Katib Journal: J Clin Oncol Date: 1998-01 Impact factor: 44.544
Authors: Lars Pache; Miriam S Dutra; Adam M Spivak; John M Marlett; Jeffrey P Murry; Young Hwang; Ana M Maestre; Lara Manganaro; Mitchell Vamos; Peter Teriete; Laura J Martins; Renate König; Viviana Simon; Alberto Bosque; Ana Fernandez-Sesma; Nicholas D P Cosford; Frederic D Bushman; John A T Young; Vicente Planelles; Sumit K Chanda Journal: Cell Host Microbe Date: 2015-09-09 Impact factor: 21.023
Authors: Geneviève Doyon; Michele D Sobolewski; Kelly Huber; Deborah McMahon; John W Mellors; Nicolas Sluis-Cremer Journal: PLoS One Date: 2014-01-29 Impact factor: 3.240
Authors: Gilles Darcis; Anna Kula; Sophie Bouchat; Koh Fujinaga; Francis Corazza; Amina Ait-Ammar; Nadège Delacourt; Adeline Melard; Kabamba Kabeya; Caroline Vanhulle; Benoit Van Driessche; Jean-Stéphane Gatot; Thomas Cherrier; Luiz F Pianowski; Lucio Gama; Christian Schwartz; Jorge Vila; Arsène Burny; Nathan Clumeck; Michel Moutschen; Stéphane De Wit; B Matija Peterlin; Christine Rouzioux; Olivier Rohr; Carine Van Lint Journal: PLoS Pathog Date: 2015-07-30 Impact factor: 6.823