Responses to second-line cisplatin-based intraperitoneal therapy in ovarian cancer: influence of a prior response to intravenous cisplatin.

Phase II trials of second-line intraperitoneal (IP) cisplatin-based therapy in patients with ovarian cancer have demonstrated the ability of this approach to produce objective antitumor responses, including surgically defined complete responses (CRs), in individuals with persistent small-volume disease after front-line cisplatin-based intravenous (IV) treatment. To examine the influence of a prior response to systemic cisplatin on the activity of second-line IP cisplatin, we retrospectively analyzed two phase II trials of cisplatin-based IP therapy in persistent/recurrent ovarian cancer conducted at our institution. Of the 89 assessable patients on the two trials, 52 (58%) had previously responded to IV cisplatin. The overall response and CR rates to second-line IP cisplatin-based therapy in this previously responding population were 56% and 33%, respectively, compared with overall response and CR rates in the 37 nonresponders to IV cisplatin of 11% and 3%, respectively (P less than .001; chi 2, 1 df). In the 36 patients responding to systemic cisplatin and whose largest tumor mass measured less than 1 cm at IP cisplatin initiation, a 42% CR rate was observed, compared with a 7% CR rate in the 14 patients with the same bulk of disease who had previously failed to respond to systemic cisplatin (P less than .025). We conclude that a prior response to systemic cisplatin strongly influences the antineoplastic activity of second-line IP cisplatin in ovarian cancer.

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Point: Intraperitoneal Chemotherapy in the Management of Ovarian Cancer

Journal of the National Comprehensive Cancer Network ◽

10.6004/jnccn.2004.0045 ◽

2004 ◽

Vol 2 (6) ◽

pp. 549-554 ◽

Cited By ~ 1

Author(s):

Maurie Markman

Keyword(s):

Ovarian Cancer ◽

Small Volume ◽

Advanced Ovarian Cancer ◽

Phase Iii ◽

Rational Approach ◽

Pharmacokinetic Studies ◽

Phase Ii Trials ◽

Intraperitoneal Therapy ◽

Phase Iii Trials ◽

Optimal Approach

Both preclinical considerations and results of phase I safety and pharmacokinetic studies provided support for the argument that intraperitoneal antineoplastic drug delivery should be a rational approach to the management of ovarian cancer. Subsequently conducted phase II trials exploring regional treatment revealed surgically documented objective responses when the approach was employed as a second-line therapy. Recently, the results of three randomized phase III trials have shown that the use of primary cisplatin-based intraperitoneal therapy leads to superior survival compared with intravenous cisplatin-based treatment in patients with small-volume residual advanced ovarian cancer after initial surgical cytoreduction. Further exploration of this unique management strategy is indicated to develop an optimal approach that maintains the demonstrated enhanced efficacy while reducing the toxicity (principally because of cisplatin) of treatment.

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Docetaxel and oxaliplatin in the second-line treatment of platinum-sensitive recurrent ovarian cancer: a phase II study

Annals of Oncology ◽

10.1093/annonc/mdm136 ◽

2007 ◽

Vol 18 (8) ◽

pp. 1348-1353 ◽

Cited By ~ 18

Author(s):

G Ferrandina ◽

M Ludovisi ◽

R De Vincenzo ◽

V Salutari ◽

D Lorusso ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Recurrent Ovarian Cancer ◽

Line Treatment ◽

Second Line ◽

Platinum Sensitive

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8004 ORAL Safety and Efficacy Outcomes in Heavily and Non-heavily Pretreated Patients With Recurrent Ovarian Cancer (ROC) After Single-agent Trabectedin Treatment – Pooled Analysis of Phase II Trials

European Journal of Cancer ◽

10.1016/s0959-8049(11)72092-5 ◽

2011 ◽

Vol 47 ◽

pp. S528-S529 ◽

Cited By ~ 2

Author(s):

N. Colombo ◽

J.M. Del Campo ◽

J. Sehouli ◽

C. Sessa ◽

M. Bidzinski ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase Ii ◽

Single Agent ◽

Recurrent Ovarian Cancer ◽

Pooled Analysis ◽

Phase Ii Trials ◽

Safety And Efficacy ◽

Heavily Pretreated ◽

Pretreated Patients

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A phase II study of weekly gemcitabine and docetaxel in first and second line metastatic breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.10668 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 10668-10668

Author(s):

C. Isaacs ◽

A. Wang ◽

R. Warren ◽

M. Wilkinson ◽

G. Grana ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Phase Ii ◽

Combination Chemotherapy ◽

Response Rate ◽

Metastatic Breast ◽

Second Line ◽

Phase Ii Trials ◽

Overall Response ◽

Metastatic Setting

10668 Background: Combination chemotherapy for metastatic breast cancer has generally been demonstrated to be associated with a higher response rate than single agent therapy, however such therapy is often accompanied by increased toxicity. Thus there is a need to develop well-tolerated combination chemotherapy regimens. Gemcitabine and docetaxel are both active agents in the treatment of this disease, and are effective and well tolerated when administered on a weekly basis. The purpose of this study was to evaluate the therapeutic efficacy and toxicity of weekly gemcitabine and docetaxel as first or second line treatment of metastatic breast cancer (MBC). Methods: Patients with measurable MBC who had received no more than 1 prior chemotherapy regimen in the metastatic setting were treated with gemcitabine 800 mg/m2 and docetaxel 30 mg/m2 on days 1 and 8 every 21 days without growth factor support. Results: Thirty-one patients were enrolled. Twenty-nine patients were evaluable for toxicity and 25 for efficacy. Median age was 55 (range 30 to 79). Visceral disease was the dominant site in 74% of patients. Doxorubicin and paclitaxel were previously administered in 74% and 48% of patients respectively. The overall response rate was 56% (complete response in 1 patient and partial responses in 13 patients). Stable disease was evident in 10 additional patients (38.4%). The progression free survival was 35 weeks (range 9 to 101 weeks) and the median overall survival was 17 months. Treatment was well tolerated with the majority of toxicities being grade 1 or 2 (85%). The only grade 3 (G3) or 4 (G4) toxicities observed were neutropenia in 14 participants (G3 41%; G4 7%), anemia in 4 (13%), G3 elevated transaminases in 3 (10%), G3 thrombocytopenia in 1 (3%), G3 flu-like symptoms in 2 (7%) and G3 edema in 1 (3%). Conclusions: The regimen of gemcitabine 800 mg/m2 and docetaxel 30 mg/m2 given two weeks out of three for MBC showed excellent overall response of 56% with very good tolerability. The findings from our trial compare well to the response rates of 36% to 79% seen in prior phase II trials utilizing higher doses of this combination chemotherapy. [Table: see text]

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179 A phase II second line study of liposomal doxorubicin and carboplatin in patients with recurrent ovarian cancer with a disease free interval equal or greater than 6 months

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(03)90212-6 ◽

2003 ◽

Vol 1 (5) ◽

pp. S57

Author(s):

D.A. Vorobiof ◽

B.L. Rapoport ◽

R. Mahomed ◽

A. Uys ◽

C. Slabber ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase Ii ◽

Liposomal Doxorubicin ◽

Recurrent Ovarian Cancer ◽

Second Line ◽

Disease Free Interval ◽

Free Interval ◽

Disease Free

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Phase I study combining olaparib and tremelimumab for the treatment of women with BRCA-deficient recurrent ovarian cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e17052 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e17052-e17052 ◽

Cited By ~ 2

Author(s):

Sarah Foster Adams ◽

Olivier Rixe ◽

Ji-Hyun Lee ◽

Dennis J. McCance ◽

Sheri Westgate ◽

...

Keyword(s):

Ovarian Cancer ◽

Adverse Events ◽

Phase I ◽

Phase Ii ◽

Immune Checkpoint ◽

Phase I Study ◽

Immune Therapy ◽

Recurrent Ovarian Cancer ◽

Parp Inhibition ◽

Phase Ii Trials

e17052 Background: With evidence that BRCA dysfunction is associated with increased T cell recruitment to tumor sites, and that PARP-inhibition may increase the immunogenicity of tumor cells, we evaluated the combination of a PARP-inhibitor and CTLA4 immune checkpoint antibody in BRCA1- ovarian cancer models. Our results demonstrated significant therapeutic synergy and durable treatment responses in preclinical studies. Based on this, a Phase I study was conducted to assess the tolerability of this regimen in women with BRCA mutation-associated recurrent ovarian cancer. Methods: Eligibility criteria included a documented BRCA1 or BRCA2 germline mutations and a diagnosis of recurrent ovarian, tubal, or primary peritoneal cancer with measurable disease. Both platinum-sensitive and platinum resistant patients were eligible. Patients with prior exposure to PARP-inhibitors or to immune therapy with the exception of CTLA4 antibodies were also eligible. Exclusion criteria included current use of anti-inflammatory agents or a prior history of autoimmune disease. Treatment consisted of Olaparib at 300mg twice daily, as well as monthly infusions of Tremelimumab at a dose of 10mg/kg, with plans for a dose reduction if toxicity was encountered. Patients completing two full treatment cycles were evaluated for evidence of toxicity, particularly immune-related adverse events, to define a dose for Phase II testing. Results: Three women were treated at the starting dose of 300mg BID of Olaparib and 10mg/kg monthly of Tremelimumab for two cycles without evidence of any dose-limiting toxicities or grade 3 adverse events. All patients experienced grade 1 and 2 toxicities, including immune related toxicities consistent with prior studies of immune checkpoint inhibitors. All three patients showed evidence of treatment response by cycle 3 based on CA125 levels and a decrease in tumor size on CT scans. Conclusions: The combination of PARP-inhibition and CTLA-4 blockade is tolerable in heavily pre-treated women with recurrent BRCA-associated ovarian cancer. Preliminary results also demonstrate evidence of therapeutic effect, supporting ongoing evaluation of this regimen in Phase II trials. Clinical trial information: NCT02571725.

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Phase II study of intraperitoneal cisplatin plus systemic etoposide as second-line treatment in patients with small volume residual ovarian cancer

European Journal of Cancer ◽

10.1016/0959-8049(94)00516-8 ◽

1995 ◽

Vol 31 (5) ◽

pp. 709-713 ◽

Cited By ~ 10

Author(s):

R.S. de Jong ◽

P.H.B. Willemse ◽

H. Boonstra ◽

E.G.E. de Vries ◽

W.T.A. van der Graaf ◽

...

Keyword(s):

Ovarian Cancer ◽

Phase Ii ◽

Small Volume ◽

Phase Ii Study ◽

Line Treatment ◽

Second Line

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A phase II study of intravenous (IV) and intraperitoneal (IP) paclitaxel (Tax), IP cisplatin (Cis), and IV bevacizumab (Bev) as first-line chemotherapy for optimal stage II or III ovarian, primary peritoneal, and fallopian tube cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.5523 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 5523-5523 ◽

Cited By ~ 3

Author(s):

J. A. Konner ◽

K. Fallon ◽

S. Pezzuli ◽

A. Iasonos ◽

P. Sabbatini ◽

...

Keyword(s):

Ovarian Cancer ◽

Abdominal Pain ◽

Fallopian Tube ◽

Phase Ii ◽

Recurrent Ovarian Cancer ◽

Stage Ii ◽

Phase Ii Trials ◽

Fallopian Tube Cancer ◽

Peritoneal Cancer ◽

Grade 3

5523 Background: IP Cis plus IV/IP Tax is a standard therapy for optimally debulked ovarian cancer. Bev is a recombinant humanized IgG1 monoclonal antibody directed against vascular endothelial growth factor (VEGF). Activity of Bev against recurrent ovarian cancer has been reported in phase II trials. In this study IP Cis and IV/IP Tax are combined with IV Bev as front-line therapy to assess safety and tolerability. Methods: Patients with optimal (<1 cm residual), FIGO stage II or III, epithelial ovarian, fallopian tube, or peritoneal cancer, acceptable organ function, and KPS = 70% are eligible. Patients receive 6 cycles of chemotherapy plus Bev (starting cycle 2): Tax 135 mg/m2 IV over 3 hours on Day 1, Cis 75 mg/m2 IP on Day 2, Tax 60 mg/m2 IP on Day 8, Bev 15 mg/kg IV on Day 1. Extended treatment with Bev is continued every 3 weeks for 17 treatments after chemotherapy is complete. The study will enroll 41 patients. The primary endpoint is safety and tolerability, determined by the proportion of patients who complete the prescribed 6 cycles of cytotoxic chemotherapy without discontinuation and without dose-limiting non-hematologic and non-electrolyte toxicity. A stopping rule will be applied if excessive toxicity is encountered. Results: To date, 8 women have been treated on the study. Median age: 53 (48–59). All 31 planned doses of chemotherapy have been administered in full. One dose of IP Tax was delayed for 2 days due to abdominal pain. One patient had her first dose of Bev delayed for 1 cycle due to surgical wound infection. There have been no toxicities > grade 3. Grade 1/2 toxicities include: fatigue (87.5%); nausea (50%); and hypomagnesemia (37.5%). Grade 3 toxicities per patient: fatigue (12.5%); hyponatremia (25%); hypokalemia (25%); hypertension (12.5%); abdominal pain (12.5%); and neutropenia (12.5%). Of the 5 patients with pretreatment CA125 >35 Units/mL, 4 normalized their value after 1 cycle of chemotherapy and 1 patient normalized after 2 cycles. Conclusions: Preliminary experience suggests that the combination of IV Bev with IP Cis plus IV/IP Tax may be well tolerated. Enrollment continues and updated results will be presented. No significant financial relationships to disclose.

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