Relationships between carboplatin exposure and tumor response and toxicity in patients with ovarian cancer.

1992 ◽  
Vol 10 (4) ◽  
pp. 520-528 ◽  
Author(s):  
D I Jodrell ◽  
M J Egorin ◽  
R M Canetta ◽  
P Langenberg ◽  
E P Goldbloom ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Response ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Area Under The Curve ◽  
Advanced Ovarian Cancer ◽  
High Dose ◽  
The Relationship ◽  
Carboplatin Auc

PURPOSE The study was undertaken to define the relationship between tumor response and carboplatin area under the curve (AUC) in patients with ovarian cancer; to study the relationship between carboplatin AUC and myelosuppression in the same population; to establish the true impact of carboplatin AUC, prior therapy, and pretreatment platelet and WBC counts on toxicity; and to define an optimal carboplatin exposure for treating patients with ovarian cancer. METHODS With the equation AUC = dose/(glomerular filtration rate [GFR]+25), carboplatin AUC (course 1) was calculated for 1,028 patients (450 previously untreated) who received single-agent carboplatin (40 to 1,000 mg/m2) for advanced ovarian cancer. GFR was measured (chromium-51-edathamil [51Cr-EDTA] or creatinine clearance) in all patients. RESULTS Regression analysis showed that carboplatin AUC, prior treatment, and Eastern Cooperative Oncology Group grade performance status (PS) are predictors of tumor response, thrombocytopenia, and leukopenia. Pretreatment platelet and WBC counts are additional predictors of thrombocytopenia and leukopenia, respectively. Although the likelihood of tumor response increased with increasing carboplatin AUC, this relationship was nonlinear. In all patient subsets, the likelihood of complete response (CR) or overall response did not increase significantly above a carboplatin AUC of 5 to 7 mg/mL x minutes. At any given carboplatin AUC, thrombocytopenia occurred more frequently than leukopenia, although both approached 100% as carboplatin AUC increased. Both thrombocytopenia and leukopenia were more frequent in pretreated than in untreated patients regardless of pretreatment count. At any carboplatin AUC, the influence of PS on likelihood of response and toxicity was profound. CONCLUSION Carboplatin dosing by AUC will lead to more predictable toxicity, and increasing carboplatin AUC above 5 to 7 mg/mL x minutes does not improve the likelihood of response but does increase myelotoxicity. Therefore, careful evaluation of high-dose carboplatin therapy in a prospective, randomized trial is needed before such treatment becomes accepted practice.

Multicenter Phase 2 Study of Combined Gemcitabine and Epirubicin as Second-Line Treatment for Patients With Advanced Ovarian Cancer

2010 ◽  
Vol 20 (6) ◽  
pp. 953-957 ◽  
Author(s):  
Viviana Murgia ◽  
Roberto Sorio ◽  
Claudia Griso ◽  
Orazio Caffo ◽  
Carmela Arcuri ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Ovarian Cancer ◽  
Hematological Toxicity ◽  
Line Treatment ◽  
Second Line ◽  
Phase 2 ◽  
Platinum Resistant ◽  
Gynecology And Obstetrics

Objective:The aim of this phase 2 trial was to evaluate the tolerability and efficacy of combined gemcitabine (G) and epirubicin (E) as second-line treatment for patients with advanced ovarian cancer.Methods:Treatment with G 1000 mg/m2 (days 1 and 8) and E 60 mg/m2 (day 1) every 3 weeks for 3 or, in the absence of progression, 6 courses.Results:Fifty patients with advanced ovarian cancer (31 serous, 2 endometrioid, 10 unclassified adenocarcinoma, and 7 other) and a median age of 60 years (range, 38-74 years) were enrolled after giving their informed consent. Performance status according to the Eastern Cooperative Oncology Group was 0 in 29 patients (58%), 1 in 17 patients (34%), and 2 in 4 patients (8%), and the initial stages according to the International Federation of Gynecology and Obstetrics were I to II in 4 patients (8%), III in 31 patients (62%), and IV in 15 patients (30%). They had previously received a median of 1.5 lines of treatment (range, 1-4). The median platinum-free interval was 5 months (range, 0-12 months): 32 patients had relapse within 6 months and 18 patients had relapse after 6 months.The response rate was 42% (2% complete response and 40% partial response), with a median duration of 7.2 months: the corresponding figures were 37.5% and 5.2 months in the platinum-resistant patients and 50% and 8.8 months in the platinum-sensitive patients. The main grade 3 to 4 hematological toxicity was neutropenia (56% of cases). After a median follow-up of 13.5 months, median progression-free survival was 5 months, and median overall survival was 23.5 months.Conclusions:This E + G combination seems to be active and safe in platinum-resistant/refractory patients.

Phase II Study of Carboplatin, Paclitaxel, and Bevacizumab With Maintenance Bevacizumab As First-Line Chemotherapy for Advanced Müllerian Tumors

2010 ◽  
Vol 28 (1) ◽  
pp. 154-159 ◽  
Author(s):  
Richard T. Penson ◽  
Don S. Dizon ◽  
Stephen A. Cannistra ◽  
Maria R. Roche ◽  
Carolyn N. Krasner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Single Agent ◽  
Area Under The Curve ◽  
Advanced Ovarian Cancer ◽  
Progression Free Survival ◽  
Ca 125 ◽  
Open Label ◽  
Peritoneal Cancer ◽  
Open Label Phase

Purpose New strategies are needed to improve outcomes for patients with advanced ovarian cancer. Bevacizumab is a recombinant humanized monoclonal antibody that neutralizes vascular endothelial growth factor but is associated with GI perforations (GIPs) in patients with recurrent disease. Patients and Methods An open-label, phase II clinical trial was conducted in newly diagnosed patients with stage ≥ IC epithelial müllerian tumors. Patients received intravenous (IV) carboplatin (area under the curve = 5), paclitaxel (175 mg/m2 IV), and bevacizumab (15 mg/kg IV) for six to eight cycles on day 1 every 21 days. Bevacizumab was omitted in the first cycle and continued as a single agent for 1 year. Results Sixty-two women participated in this study. Fifty-one patients (82%) were optimally surgically cytoreduced before treatment. The median age was 58 years (range, 18 to 77 years). Forty-five women (73%) had ovarian cancer, 10 (16%) had peritoneal cancer, four (6%) had fallopian tube cancers, and three (5%) had uterine papillary serous tumors. The majority of patients (90%) had stage III or IV disease. A median of 17 maintenance cycles (range, 0 to 25+ cycles) of bevacizumab (556 cycles) were administered with mild toxicity. Treatment was associated with two pulmonary embolisms and two GIPs, all occurring during the chemotherapy phase of treatment (364 total cycles). No grade 4 toxicities were seen during maintenance bevacizumab treatment. Radiographic responses were documented in 21 (75%) of 28 women with measurable disease (11 complete responses and 10 partial responses), with CA-125 responses in 76% of patients (11 complete responses, 21%; and 35 partial responses, 55%). The progression-free survival rate at 36 months was 58%. Conclusion The regimen of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab is feasible, safe, and worthy of future study in advanced ovarian cancer.

scholarly journals When Ovarian Cancer Is Not: Characterizing Nonovarian Cancer Pathology in a Laparoscopy-Based Triage System

2018 ◽  
Vol 28 (8) ◽  
pp. 1485-1490 ◽  
Author(s):  
Robert L. Dood ◽  
Nicole D. Fleming ◽  
Robert L. Coleman ◽  
Shannon N. Westin ◽  
Olivia D. Lara ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Ovarian Cancer ◽  
Percutaneous Biopsy ◽  
Histologic Diagnosis ◽  
Chemotherapy Administration ◽  
Cancer Pathology ◽  
Conclusive Diagnosis

ObjectiveEstablishing an accurate histologic diagnosis is essential for determining the appropriate course of therapy for ovarian cancer. This study sought to investigate and describe nonovarian cancer pathologies discovered during the systematic laparoscopic workup of presumed advanced ovarian cancer.MethodsA retrospective cohort of patients with presumed advanced ovarian cancer (based on elevated CA125 and/or imaging) presenting to our center without confirmed pathologic diagnosis were identified and characterized. Patients without ovarian cancer on final pathology were described and compared with those with confirmed epithelial ovarian cancer using standard statistical methods.ResultsNonovarian cancer was found in 26 (7.1%) of 365 cases over 3.5 years of study, and included benign ovarian pathology, and metastatic uterine, breast, and gastrointestinal cancers. Most nonovarian cancer cases could not be diagnosed with percutaneous biopsy, and instead used diagnostic laparoscopy or assessment at the time of laparotomy for diagnosis (58%). No patient received inappropriate treatment. Nonovarian cancer cases were more likely to be nonwhite (P = 0.003), have a better Eastern Cooperative Oncology Group performance status (P < 0.001), and have a lower CA125 value (P < 0.001), and were less likely to have pleural effusions (P = 0.04).ConclusionsA systematic laparoscopic triage approach to advanced-stage ovarian cancer eliminates incorrect neoadjuvant chemotherapy administration and inappropriate laparotomy. This algorithm identified a population of women who are more likely to have nonovarian cancer pathology. Increasing screening efforts should be focused on conclusive diagnosis with the least invasive testing possible.

Oxaliplatin or Paclitaxel in Patients With Platinum-Pretreated Advanced Ovarian Cancer: A Randomized Phase II Study of the European Organization for Research and Treatment of Cancer Gynecology Group

2000 ◽  
Vol 18 (6) ◽  
pp. 1193-1202 ◽  
Author(s):  
Martine J. Piccart ◽  
John A. Green ◽  
Angel Jimenez Lacave ◽  
Nick Reed ◽  
Ignace Vergote ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Time To Progression ◽  
European Organization ◽  
Randomized Phase Ii ◽  
Grade 3

PURPOSE: This was a multicentric, open, randomized, phase II study of single-agent paclitaxel and oxaliplatin to evaluate the efficacy of oxaliplatin in a relapsing progressive ovarian cancer patient population and to analyze the safety profile and impact of both agents on quality of life, time to progression, and survival. PATIENTS AND METHODS: Eighty-six patients with platinum-pretreated advanced ovarian cancer were randomly assigned to two arms: 41 received paclitaxel at 175 mg/m2 over 3 hours every 3 weeks, and 45 received oxaliplatin at 130 mg/m2 over 2 hours every 3 weeks. For inclusion, patients had to have a performance status of 0 to 2 and to have received at least one and no more than two prior cisplatin- and/or carboplatin-containing chemotherapy regimens within the last 12 months. RESULTS: Seven confirmed responses were observed in each arm, for an overall response rate in the total treated population of 17% (95% confidence interval [CI], 7% to 32%) in the paclitaxel arm and 16% (95% CI, 7% to 29%) in the oxaliplatin arm. Median time to progression was 14 weeks and 12 weeks, and overall survival was 37 weeks and 42 weeks in the paclitaxel and oxaliplatin arms, respectively. Among 63 patients with a 0- to 6-month progression-free, platinum-free interval, there were five objective responses with paclitaxel in 31 patients and two objective responses with oxaliplatin in 32 patients. Nine patients (22%) in the paclitaxel arm had grade 3 or 4 neutropenia (National Cancer Institute of Canada [NCIC] Common Toxicity Criteria). Two patients (4%) experienced grade 3 thrombocytopenia in the oxaliplatin arm. Maximum grade (grade 3) NCIC neurosensory toxicity was experienced by three patients (7%) in the paclitaxel arm and by four patients (9%) in the oxaliplatin arm. CONCLUSION: Single-agent oxaliplatin at 130 mg/m2 every 3 weeks is active with moderate toxicity in patients with cisplatin-/carboplatin-pretreated advanced ovarian cancer.

Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group.

1992 ◽  
Vol 10 (5) ◽  
pp. 718-726 ◽  
Author(s):  
K Swenerton ◽  
J Jeffrey ◽  
G Stuart ◽  
M Roy ◽  
G Krepart ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Response Rate ◽  
Residual Disease ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Ovarian Cancer ◽  
Phase Iii ◽  
Treatment Center ◽  
Clinical Response Rate ◽  
Time To Progression

PURPOSE Given the potential for improved tolerance, a trial was initiated to compare the toxicity and efficacy of a standard regimen of cisplatin-cyclophosphamide (75 mg/m2 and 600 mg/m2, respectively) with an experimental regimen of carboplatin-cyclophosphamide (300 mg/m2 and 600 mg/m2, respectively) in women with postoperative macroscopic residual ovarian cancer. PATIENTS AND METHODS Between 1985 and 1989, 447 (417 eligible) patients were randomized. Treatment arms were well balanced; most patients had stage III (82%), grade 3 (54%) tumors with bulky residual (greater than 2 cm in 59%), and good performance status (Eastern Cooperative Oncology Group [ECOG] 0 or 1, 77%). Response was assessed after six 4-week cycles. RESULTS The treatments were equally deliverable, with 76% of patients completing their allocated regimen. The reported reasons for failure to complete treatment differed; toxicity/refusal predominated on the cisplatin arm, and progressive disease predominated on the carboplatin arm (P = .0092). Cisplatin-treated patients were more likely to develop neuropathy and nephropathy, and carboplatin patients experienced myelosuppression, particularly thrombocytopenia. Efficacy was similar, with no significant differences for the cisplatin and carboplatin arms in clinical response rate (57% v 59% in those with measurable disease), pathologic response rate (52% v 54% in those suitable for relaparotomy), time to progression (median, 56 v 58 weeks), or overall survival (median, 100 weeks v 110 weeks). Time to progression and survival were predicted by residual disease size, performance status, and treatment center (with those treated at centers that accrued more patients doing better). CONCLUSION Neither regimen is optimal in that relapse remains the norm. It may be inappropriate to expect that any single regimen can be an effective therapy for all patients with advanced ovarian cancer. Both cisplatin and carboplatin are likely to have a role in future treatment strategies.

Impact of cyclophosphamide on relationships between carboplatin exposure and response or toxicity when used in the treatment of advanced ovarian cancer.

1993 ◽  
Vol 11 (6) ◽  
pp. 1156-1164 ◽  
Author(s):  
L M Reyno ◽  
M J Egorin ◽  
R M Canetta ◽  
D I Jodrell ◽  
K D Swenerton ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Drug Exposure ◽  
Single Agent ◽  
Advanced Ovarian Cancer ◽  
Dose Intensity ◽  
Time Curve ◽  
University Of Maryland ◽  
Grade 3 ◽  
The Impact ◽  
Carboplatin Auc

PURPOSE To determine (1) the impact of cyclophosphamide 600 mg/m2 on previously defined relationships between carboplatin area under the plasma concentration versus time curve (AUC) and indices of toxicity and response in women with advanced ovarian cancer; and (2) the relationships between indices of cumulative drug exposure and clinical outcomes. METHODS Carboplatin AUC = dose/(creatinine clearance [CCr] + 25) and was calculated in 224 women who received carboplatin 300 mg/m2 and cyclophosphamide 600 mg/m2. The likelihood of grade 3 or greater myelotoxicity at any carboplatin AUC was compared with the likelihood of myelotoxicity at the same single-agent carboplatin AUC. The nadir count predicted using the University of Maryland single-agent carboplatin dosing formula was compared with the nadir count observed. Received and relative-received dose-intensity were calculated. Carboplatin exposure-intensity was defined by substituting cumulative carboplatin exposure for total dose. Relationships were sought between these indices and therapeutic outcomes. RESULTS The incidence of leukopenia and thrombocytopenia at any carboplatin AUC was greater for the two-drug combination than for single-agent carboplatin. The platelet nadir in 83% of patients was less than or equal to the nadir predicted for the same single-agent carboplatin AUC. Despite a narrow range of received dose-intensities, carboplatin exposure-intensity was distributed over a twofold range. There were no relationships between received and relative-received dose-intensity or carboplatin exposure-intensity and time to progression or survival. CONCLUSION Any carboplatin AUC when administered with cyclophosphamide 600 mg/m2 produces greater myelotoxicity than the same AUC of single-agent carboplatin. Received carboplatin dose-intensity underestimates the range of plasma drug exposure resulting from a fixed carboplatin dosing regimen. Whether higher carboplatin exposures can improve outcome requires prospective validation.

High dose single-agent paclitaxel in a hemodialysis patient with advanced ovarian cancer: a case report with pharmacokinetic analysis and review of the literature

2008 ◽  
Vol 18 (3) ◽  
pp. 564-570 ◽  
Author(s):  
M. BAUR ◽  
B. FAZENY-DOERNER ◽  
S. J. OLSEN ◽  
C. DITTRICH
Keyword(s):  
Ovarian Cancer ◽  
Plasma Concentration ◽  
Peak Plasma ◽  
Single Agent ◽  
Objective Response ◽  
Advanced Ovarian Cancer ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
Severe Toxicity

There exists only scarce data on the pharmacokinetics of paclitaxel in patients with renal insufficiency. A 53-year-old woman on hemodialysis was treated with paclitaxel for relapsed ovarian cancer. Paclitaxel was administered as a 3-h infusion at 175, 225, and 300 mg/m2 on nonhemodialysis days. The pharmacokinetic analysis revealed independence of the pharmacokinetic parameters for paclitaxel from the extent of renal (dys-)function. The peak plasma concentration of the 300 mg/m2 dose level before and after dialysis was 23.05 and 21.01 ng/mL, respectively, proving that paclitaxel was not dialysable. The area under the plasma concentration versus time curve for the standard and highest dose of paclitaxel was 12,200 ng·h/mL in mean and 40,936 ng·h/mL, respectively. The absence of marked side effects at all dose levels was in line with the independence of the pharmacokinetic parameters for paclitaxel from renal function. No objective response was found, but a marked improvement of symptoms from gastrointestinal obstruction as well as a decrease in the serum CA125 level were observed. Patients with terminal renal failure undergoing hemodialysis tolerate conventional and even high doses of paclitaxel without experiencing severe toxicity.

Efficacy of anlotinib in advanced soft tissue sarcoma by age, gender, and ECOG performance status.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e23562-e23562
Author(s):  
Zhiwei Fang ◽  
Yang Yao ◽  
Jianqiang Cai ◽  
Yihebali Chi ◽  
Shusen Wang ◽  
...  
Keyword(s):  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Ecog Performance Status ◽  
Free Survival ◽  
Cautious Interpretation ◽  
Ecog Ps ◽  
The Relationship ◽  
Clinical Trial Information

e23562 Background: ALTER0203 was a randomized phase IIB trial (NCT02449343) that demonstrated single-agent activity of anlotinib in advanced STS (aSTS). The primary endpoint progression-free survival (PFS) was met and presented as an oral presentation in 2018 ASCO. We evaluated the relationship between age, gender and ECOG performance status. Methods: Median PFS was analyzed in subgroups of age (≤40 y; > 40 y), gender (male; female) and ECOG performance status score (0; 1). All analyses were exploratory and required cautious interpretation. Results: A total of 158 patients received anlotinib in the ALTER0203 study. 79 patients (50.0%) were > 40 y. Median PFS was longer in patients of age > 40 y than ≤40 y (7.43 vs 5.43 months, P = 0.40). In patients receiving anlotinib, 76 patients (48.1%) were female and median PFS was longer in female than male (9.80 vs 4.43 months, P = 0.002). All enrolled patients had a Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. 107 patients (67.7%) were with poor PS (ECOG PS = 1). The median PFS was longer in PS of 1(8.43 vs 4.73, P = 0.53) than PS of 0. Conclusions: In patients receiving anlotinib, longer mPFS was observed in patients of age > 40 y, ECOG PS = 1 and female. Clinical trial information: NCT02449343 .

Efficacy of Sequential High-Dose Doxorubicin and Ifosfamide Compared With Standard-Dose Doxorubicin in Patients With Advanced Soft Tissue Sarcoma: An Open-Label Randomized Phase II Study of the Spanish Group for Research on Sarcomas

2009 ◽  
Vol 27 (11) ◽  
pp. 1893-1898 ◽  
Author(s):  
Joan Maurel ◽  
Antonio López-Pousa ◽  
Ramón de las Peñas ◽  
Joaquín Fra ◽  
Javier Martín ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Soft Tissue Sarcoma ◽  
Standard Dose ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
High Dose ◽  
Open Label ◽  
Advanced Soft Tissue Sarcoma ◽  
Ecog Performance Status

Purpose To assess the progression-free survival (PFS) and antitumor response to standard-dose doxorubicin compared with sequential dose-dense doxorubicin and ifosfamide in first-line treatment of advanced soft tissue sarcoma. Patients and Methods Patients with measurable advanced soft tissue sarcoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2, between the ages 18 and 65 years, and with adequate bone marrow, liver, and renal function were entered in the study. The stratifications were: ECOG PS (0 v 1), location of metastases, and potentially resectable disease. Patients were randomly assigned to either doxorubicin 75 mg/m2 given as a bolus injection every 3 weeks for 6 cycles (arm A) or doxorubicin at 30 mg/m2 per day for 3 consecutive days once every 2 weeks for 3 cycles followed by ifosfamide at 12.5 g/m2 delivered by continuous infusion over 5 days once every 3 weeks for 3 cycles with filgastrim or pegfilgastrim support (arm B). Results Between December 2003 and September 2007, 132 patients were entered onto the study. Febrile neutropenia, asthenia, and mucositis were more frequent in the arm B. The interim preplanned analysis for futility allowed the premature closure. Objective responses were observed in 23.4% of assessable patients in arm A and 24.1% in arm B. PFS was 26 weeks in the arm A and 24 weeks in arm B (P = .88). Overall survival did not differ between the two therapeutic arms (P = .14). Conclusion Single-agent doxorubicin remains the standard treatment in fit patients with advanced soft tissue sarcoma.

Combination Targeted Therapy With Sorafenib and Bevacizumab Results in Enhanced Toxicity and Antitumor Activity

2008 ◽  
Vol 26 (22) ◽  
pp. 3709-3714 ◽  
Author(s):  
Nilofer S. Azad ◽  
Edwin M. Posadas ◽  
Virginia E. Kwitkowski ◽  
Seth M. Steinberg ◽  
Lokesh Jain ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Cell Cancer ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Response Duration ◽  
Clinical Activity ◽  
Therapeutic Effects ◽  
Vegf Receptor

PurposeSorafenib inhibits Raf kinase and vascular endothelial growth factor (VEGF) receptor. Bevacizumab is a monoclonal antibody targeted against VEGF. We hypothesized that the complementary inhibition of VEGF signaling would have synergistic therapeutic effects.Patients and MethodsPatients had advanced solid tumors, Eastern Cooperative Oncology Group performance status of 0 to 1, and good end-organ function. A phase I dose-escalation trial of sorafenib and bevacizumab was initiated at below-recommended single-agent doses because of possible overlapping toxicity: sorafenib 200 mg orally twice daily and bevacizumab intravenously at 5 mg/kg (dose level [DL] 1) or 10 mg/kg (DL2) every 2 weeks. Additional patients were enrolled at the maximum-tolerated dose (MTD).ResultsThirty-nine patients were treated. DL1 was the MTD and administered in cohort 2 (N = 27). Dose-limiting toxicity in DL2 was grade 3 proteinuria and thrombocytopenia. Adverse events included hypertension, hand-foot syndrome, diarrhea, transaminitis, and fatigue. Partial responses (PRs) were seen in six (43%) of 13 patients with ovarian cancer (response duration range, 4 to 22+ months) and one of three patients with renal cell cancer (response duration, 14 months). PR or disease stabilization ≥ 4 months (median, 6 months; range, 4 to 22+ months) was seen in 22 (59%) of 37 assessable patients. The majority (74%) required sorafenib dose reduction to 200 mg/d at a median of four cycles (range, one to 12 cycles).ConclusionCombination therapy with sorafenib and bevacizumab has promising clinical activity, especially in patients with ovarian cancer. The rapidity and frequency of sorafenib dose reductions indicates that sorafenib at 200 mg twice daily with bevacizumab 5 mg/kg every 2 weeks may not be tolerable long term, and alternate sorafenib dosing schedules should be explored.

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