Integration of neuropathy-sparing multimetronomic bevacizumab and multibiochemical modulation followed by regional consolidation and maintenance therapy for refractory ovarian cancer

• Published in: Journal of clinical oncology Vol. 30; no. 15_suppl; p. e15576
• Main Authors: Bruckner, Howard, Brandeis, Alison Emily, Radjabi, Amir Reza, Mull, Ruslan, Stega, Jeanetta, Hirschfeld, Azriel
• Format: Journal Article
• Language: English
• Published: 20.05.2012
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2012.30.15_suppl.e15576

Abstract only e15576 Background: In vitro disease models predicted advantages for use of 1/2-1/4 standard cytotoxic doses and selection of drugs each of which simultaneously interact with multiple drugs. Methods: Treatment (rx) combined 10mg/kg bevacizumab (B) q 2 weeks, cyclophosphamide (Cy) 400mg/m 2 modified AC (Garcia Gyn Onc 05) with low dose GFLIP (carboplatin=P) P -/+ docetaxel (D) (Bruckner, ASCO 08). Regional therapy followed: +/- intraperitoneal, target directed or D+cisplatin, +/- or empirical HIPEC. To prevent further neuropathy, present in 8 of 10 pts, D was reserved for late addition (as needed) to create less than 0.5cm or otherwise “eligible for reduction surgery” tumors. Results: Overall S is 8/10 and 4/6 @ 6 and 12 mos. Two lead pts S at 18+ mos. 10/10 tumor marker responses (R); 9/10 objective R all with benefit. Patients (pts) had failed a median of 3 prior regimens and all had large rapidly worsening tumors during prior rx; 6/10 were considered “entirely untreatable.” There were no grade 4 complicated AEs, other than anemia. Epistaxis and HTN were minor, easily controlled AEs. Three deaths due to disease: One pt, PS3, refused surgery for a preexisting bowel obstruction and one, PS3, required weekly paracentesis and had sb obstruction. She relapsed after four mos OR. The third, PS4, pt was paracentesis and thorocentesis dependent and had a 6 mos OR. Median PFS is not yet reached. The lead pt, a 33yo third line, twice operated achieved a pCR in 4 mos, now stoma reversed, unmaintained for 14+ mos, following vaccine rx. Seven had OR without D; brief addition of D; brief addition of D produced 3/3 OR, a pCR, CR and PR. IRB provided prospective oversight of consent. Conclusions: This is an active multi-drug, in theory, anti BRCA rx, for very high risk and some otherwise “untreatable” pts. Simultaneous modulation of multiple drugs, both metronomically, six ways, (Cy-GFIC-D) and biochemically, up to five ways "each," 15 ways (5+4+3+2+1), is safe. Algorithms can offer cost savings (for B) by selecting a finite, short, “best” period for rx and then definitive, B free, consolidation rx. B driven response can create new windows of opportunity for test worthy multidisciplinary rxs.