Phase I and pharmacologic study of paclitaxel administered weekly in patients with relapsed ovarian cancer.

1997 ◽  
Vol 15 (1) ◽  
pp. 187-192 ◽  
Author(s):  
D Fennelly ◽  
C Aghajanian ◽  
F Shapiro ◽  
C O'Flaherty ◽  
M McKenzie ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Standard Dose ◽  
Advanced Ovarian Cancer ◽  
Dose Intensity ◽  
Maximum Tolerated Dose ◽  
Significant Activity ◽  
Weekly Schedule ◽  
The Mean

PURPOSE Paclitaxel has shown significant activity in advanced ovarian cancer. In vitro studies with paclitaxel have suggested that fractionated brief infusion schedules may be more effective than the standard 24-hour infusion. We commenced a phase I evaluation of escalating-dose paclitaxel (40, 50, 60, 80, 100 mg/m2) administered weekly as a 1-hour infusion in patients with recurrent ovarian cancer. All patients had received prior paclitaxel and cisplatin therapy. All patients received standard premedication. PATIENTS AND METHODS Eighteen patients are assessable on this phase I study. The mean age was 54 years (range, 48 to 74). The median number of prior chemotherapy regimens was three (range, two to five). The mean paclitaxel-free interval was 10.1 months (range, 1 to 24). RESULTS A total of 194 cycles of therapy were administered, with a mean of 10 (range, one to 12) per patient. No mucositis or grade III neuropathy was seen. Alopecia occurred in one out of 18 assessable patients. The mean neutrophil nadir was 4.0 x 10(9)/L. At the top dose level (100 mg/m2) delivered, dose-intensity was 90.75% of that planned and greater than two fold the standard dose-intensity. Partial responses were seen in four of 13 assessable patients (30%). Two patients with progression of disease on standard three-week paclitaxel schedules switched to a weekly schedule with demonstrated response. Increasing paclitaxel dose correlated with measured area under the curve (AUC) (R2 = .614). Dose-limiting toxicity was reached at 100 mg/m2 with two of three patients experiencing a treatment delay, thus defining a maximum-tolerated dose of 80 mg/m2 in this group of heavily pretreated patients on this weekly schedule. CONCLUSION (1) Paclitaxel administered as a 1-hour infusion is well tolerated; (2) this schedule of administration does not result in cumulative myelosuppression; and (3) this schedule of administration results in dose-intensive paclitaxel delivery with a favorable toxicity profile.

Phase I dose-finding and pharmacokinetic study of a combination of elisidepsin (E) and erlotinib (T) in patients (pts) with advanced solid tumors.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3093-3093
Author(s):  
Sanjay Goel ◽  
Teresa Moran ◽  
Cinthya Coronado ◽  
Santiago Viteri Ramirez ◽  
Imran Chaudhary ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Solid Tumors ◽  
Standard Dose ◽  
Therapeutic Option ◽  
Maximum Tolerated Dose ◽  
Dose Finding ◽  
Advanced Solid Tumors ◽  
Grade 3

3093 Background: E is a new marine compound that has shown synergism with T in vitro even in T-resistant non-small-cell lung cancer (NSCLC) cell lines. Based on these findings, a phase I clinical trial was undertaken to identify the maximum tolerated dose (MTD) and recommended dose (RD) of E (3-h iv, days 1, 8 and 15) followed by T (once daily) in 3-week cycles. Secondary objectives were evaluation of safety and feasibility, PK and preliminary efficacy results. Methods: Patients (pts) with advanced solid tumors with no standard therapeutic option were recruited. Cohorts of 3-6 pts were included at each dose level (DL), with escalating doses of E in increments of 25-50% according to toxicities, and 2 different T doses (100 and 150 mg/day). Results: Thirty pts (median age, 57 years; 19 females) were evaluable. Main tumor types included NSCLC, colorectal, melanoma, and ovarian cancer. Six DLs were assessed. Starting DL was E 0.33 mg + T 100mg. One dose-limiting toxicity (DLT) out of 6 pts (grade 3 bilirubin increase) was observed at DL3 (E 0.75 mg + T 150 mg). Another DLT (dose omissions due to ALT increase) was found at DL6 (E 2.25 mg + T 100 mg). Frequent toxicities were diarrhea (53%), nausea (23%), vomiting (33%), rash (47%), pruritus (43%), dry skin (27%) and acneiform dermatitis (17%). Grade 3/4 toxicities included diarrhea (2 pts), rash (2 pts) and pruritus (1 pts). Main biochemical abnormalities were ALT (grade 3/4 in 4 pts) and total bilirubin increase (grade 3 in 2 pts). No severe hematological abnormalities were observed. Most toxicities were related to T; therefore, T dose was reduced to 100 mg/day. No PK interaction between E and T was observed. No objective responses were reported. Six pts attained stable disease >3 months (3 NSCLC; 1 ovarian cancer, 1 colorectal cancer, 1 invasive thymoma). Conclusions: E + T was a manageable combination; however, the difficulty of combining E with the standard dose of T (150mg) and the lack of activity made this combination unattractive for further development in the current schedule. Possibly, other schedules may demonstrate more efficacy.

Phase I clinical and pharmacologic study of weekly cisplatin combined with weekly irinotecan in patients with advanced solid tumors.

1998 ◽  
Vol 16 (12) ◽  
pp. 3858-3865 ◽  
Author(s):  
L B Saltz ◽  
D Spriggs ◽  
L J Schaaf ◽  
G K Schwartz ◽  
D Ilson ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Maximum Tolerated Dose ◽  
Clinical Activity ◽  
Weekly Schedule ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
Irinotecan Dose ◽  
Pharmacologic Study

PURPOSE In vitro synergy between cisplatin and irinotecan (CPT-11) has been reported. We designed a combination schedule of these agents to maximize the potential for synergistic interaction. PATIENTS AND METHODS To maximize the opportunity for synergy, we divided the cisplatin into four consecutive weekly treatments, followed by a 2-week rest. Each dose of cisplatin was immediately followed by a dose of irinotecan. The dose of cisplatin was fixed at 30 mg/m2/wk. The initial irinotecan dose was 50 mg/m2/wk and this was escalated by 30% increments in successive cohorts of three to six patients to establish the maximum-tolerated dose (MTD). Pharmacokinetics of irinotecan and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were analyzed. RESULTS Of 35 patients with solid tumors enrolled onto this trial, 30 were assessable for toxicity and response. The MTD for this regimen was 30 mg/m2/wk of cisplatin plus 50 mg/m2/wk of irinotecan in previously treated patients and 30 mg/m2/wk of cisplatin plus 65 mg/m2/wk of irinotecan in chemotherapy-naive patients. Neutropenia was the dose-limiting toxicity (DLT) encountered in this trial. Diarrhea was infrequent and rarely dose-limiting. Seven of 30 assessable patients achieved a partial response. No alteration in irinotecan, SN-38, or SN-38G pharmacokinetics resulted from the administration of cisplatin with irinotecan. CONCLUSION The administration of cisplatin and irinotecan on this weekly schedule provides a practical and well-tolerated regimen that has the potential to maximize any clinical synergy between the two agents. Evidence of substantial clinical activity was seen in this phase I study.

Phase I Study of IMGN901 in Patients with Relapsed and Relapsed/Refractory CD56-Positive Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3689-3689 ◽  
Author(s):  
Asher Alban Chanan-Khan ◽  
Mecide Gharibo ◽  
Sundar Jagannath ◽  
Nikhil C. Munshi ◽  
Kenneth C Anderson ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase I ◽  
Phase I Study ◽  
Maximum Tolerated Dose ◽  
Preliminary Evidence ◽  
Clinical Activity ◽  
Weekly Schedule ◽  
Minor Response

Abstract Background: IMGN901 (huN901-DM1) is a novel conjugate of the cytotoxic maytansinoid, DM1, with the humanized CD56-binding monoclonal antibody, N901. Once bound to CD56 on a cancer cell, the conjugate is internalized and releases DM1. About 70% of multiple myeloma (MM) cases have surface expression of CD56. Preclinical investigations demonstrated significant in vitro and in vivo anti-myeloma activity of IMGN901. Objectives: To determine the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs), and pharmacokinetics (PK) of increasing doses of IMGN901 given for MM on a weekly schedule. Methods: Patients with relapsed or relapsed/refractory MM who have failed at least one prior therapy and have CD56-expressing MM received a single IV infusion of IMGN901 on 2 consecutive weeks every 3 weeks. Patients are enrolled in cohorts of 3 at each dose level, with DLT triggering cohort expansion. Results: Eighteen patients have received IMGN901 to date in this study - 3 patients each at 40, 60, 75, 90, 112, and 140 mg/m2/week. One patient experienced a DLT (grade 3 fatigue) on 140 mg/m2/week, and this cohort is being expanded to enroll up to 6 patients. No patients have experienced serious hypersensitivity reactions or evidence of presence of humoral responses against the huN901 antibody component (HAHA) or against the DM1 component (HADA). Preliminary PK results indicate an approximately linear relationship between dosing and observed maximal serum concentration. A confirmed minor response (MR) was documented in 3 heavily pretreated patients (1 patient each at 60, 90, and 112 mg/m2/week) using the European Bone Marrow Transplant criteria. Durable stable disease was reported at doses of 60, 90, 112, and 140 mg/m2/week. Of the 18 patients treated in the study, eight patients remained on treatment with IMGN901 for at least 15 weeks, five of these 8 patients remained on treatment for at least 24 weeks, and two of these 5 patients remained on treatment for at least 42 weeks. This phase I study provides preliminary evidence of safety as well as clinical activity of IMGN901 in patients with CD56-positive MM who have failed established MM treatments. Updated results of this ongoing study will be presented.

Phase I trial of weekly paclitaxel in advanced lung cancer.

1998 ◽  
Vol 16 (1) ◽  
pp. 153-158 ◽  
Author(s):  
W Akerley ◽  
M Glantz ◽  
H Choy ◽  
V Rege ◽  
S Sambandam ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase I ◽  
Dose Level ◽  
Objective Response ◽  
Dose Intensity ◽  
Maximum Tolerated Dose ◽  
Advanced Lung Cancer ◽  
Weekly Schedule ◽  
Grade Ii ◽  
Dose Levels

PURPOSE We conducted a phase I study in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum-tolerated dose (MTD) of paclitaxel using an extended weekly schedule. PATIENTS AND METHODS Patients with stage IIIB/IV NSCLC were treated with paclitaxel administered weekly over 3 hours for 6 weeks of an 8-week cycle. Doses were modified for granulocyte counts less than 1,800/microL or neurotoxicity greater than grade I. Groups of three patients were entered at each dose level. The dose was escalated to the next level if less than 50% of patients developed unacceptable toxicity and received more than 80% of the intended first-cycle dose. RESULTS Twenty-six patients were entered through six dose levels (100, 125, 135, 150, 175, and 200 mg/m2/wk). Four of six patients at the 175-mg/m2 dose level and only one of six patients at the 200-mg/m2 level received all scheduled doses of paclitaxel during cycle 1. Neutropenia was dose-limiting. Fourteen patients were treated with subsequent cycles of paclitaxel. Grade II to III neuropathy developed in five of 24 patients. It occurred more commonly with greater duration of therapy, but improved following dose reduction. Nine of 26 (35% +/- 10%) patients demonstrated an objective response. CONCLUSION The MTD of paclitaxel using a weekly schedule is 175 mg/m2/wk for 6 of 8 weeks. Neutropenia limits dosing acutely, but neuropathy is limiting with sustained therapy. This schedule of paclitaxel results in a twofold to threefold increase in dose-intensity with less toxicity than anticipated from conventional dosing. Further evaluation of this schedule is warranted to assess efficacy and toxicity of prolonged administration.

Phase I study of taxol and granulocyte colony-stimulating factor in patients with refractory ovarian cancer.

1992 ◽  
Vol 10 (7) ◽  
pp. 1165-1170 ◽  
Author(s):  
G Sarosy ◽  
E Kohn ◽  
D A Stone ◽  
M Rothenberg ◽  
J Jacob ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Standard Dose ◽  
Objective Response ◽  
Dose Intensity ◽  
Response To Therapy ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Current Standard ◽  
Stimulating Factor

PURPOSE To increase the taxol dose beyond the current standard dose intensity of 175 mg/m2 per 21 days in patients with refractory ovarian cancer. PATIENTS AND METHODS Fifteen patients who had platinum-refractory or recurrent advanced-stage ovarian cancer were treated with taxol in a phase I trial and were given granulocyte-colony stimulating factor (G-CSF). Taxol was administered at doses of 170, 200, 250, and 300 mg/m2 every 3 weeks. G-CSF was given as a daily subcutaneous injection that started 24 hours after the completion of the taxol infusion. RESULTS Four patients required either taxol dose reduction or delay. The dose-limiting toxicity (DLT) was peripheral neuropathy, and it occurred at 300 mg/m2. This toxicity was manifested clinically as a stocking-and-glove sensory disturbance that primarily affected proprioception, and was associated with objective changes on nerve conduction studies in affected individuals. Mucositis was rarely observed. Substantial myelosuppression was observed, but was not dose-limiting. Five of 14 assessable patients experienced an objective response to therapy, with another five individuals who experienced a 30% to 45% reduction in tumor mass. CONCLUSION Taxol can be safely administered in doses up to 250 mg/m2 with G-CSF support, which may make it possible to study taxol dose intensification.

Phase I/II study of bortezomib (B) in patients with systemic AL-amyloidosis (AL)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8050-8050 ◽  
Author(s):  
D. E. Reece ◽  
V. Sanchorawala ◽  
U. Hegenbart ◽  
G. Merlini ◽  
G. Palladini ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Escalation ◽  
Specific Inhibitor ◽  
Maximum Tolerated Dose ◽  
26S Proteasome ◽  
Al Amyloidosis ◽  
Significant Activity ◽  
Weekly Schedule ◽  
Eligibility Criteria ◽  
Previously Treated

8050 Background: AL is characterized by deposition of monoclonal immunoglobulin light chains leading to multi-organ failure and death. B (Velcade®) is a specific inhibitor of the 26S proteasome with activity in several malignancies. This mechanism of action raises concern of enhancing the amyloidogenic protein deposition and worsening of AL. This phase I/II study is to determine the maximum tolerated dose (MTD) and toxicity profile of B in pts previously treated for AL. Secondary objectives include the rate and duration of hematologic and organ responses. Methods: A 3+3 dose escalation design was used for the phase I part. Eligibility criteria included previously treated AL with organ involvement, LVEF =40% and adequate organ function. Pts with prior B treatment, infection, significant cardiac disease, bleeding or gr. 2 neuropathy were excluded. Seven cohorts are planned to examine two administration schedules. A weekly schedule administering 0.7,1.0,1.3 or 1.6 mg/m2 of B on day 1, 8, 15, 22 of a 35-day cycle. In the bi-weekly schedule, 0.7, 1.0 or 1.3 mg/m2 are given on day 1,4,8, 11 of a 21-day cycle. Pts were assessed at specified intervals and dose-limiting toxicities (DLT) were assessed during cycle 1. Results: At this time, 15 pts were treated in the 4 weekly cohorts. Median age was 59 yrs (38–74). All pts had previously received systemic therapy; 100% had received melphalan (58% with prior SCT), 83% steroids, 58% thalidomide. 75% of pts had = 2 organs involved at baseline, renal 42%, cardiac 33%, neuropathy 33%. One DLT (worsening CHF) was observed in cohort 1.6 mg/m2. Two pts discontinued early due to CHF and hypotension. Grade 3/4 AEs were reported in 42% of pts and the most frequent were fatigue 17%, infection 17%, CHF 8% and retinal detachment 8%. The most frequent grade 1/2 AEs were diarrhea 67%, nausea 42%, fever 33%, dizziness 33% and neuropathy 8%. There were no treatment-related deaths. Of the 11 evaluable pts for response, 5 (45%) had objective hematological responses (2 CR and 3 PR) and 4 pts (36%) have stable disease > 6 months. Dose escalation on the biweekly schedule is ongoing. Conclusions: B has significant activity in patients with relapsed AL in this preliminary analysis and tolerance to B is satisfactory. The MTD for the weekly schedule is 1.6 mg/m2. Further assessment is planned in the phase II part. [Table: see text]

A phase I/IB study of paclitaxel in combination with VS-6063, a focal adhesion kinase (FAK) inhibitor, in patients (pts) with advanced ovarian cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS2620-TPS2620 ◽  
Author(s):  
Suzanne Fields Jones ◽  
Kathleen N. Moore ◽  
Manish R. Patel ◽  
Jeffrey R. Infante ◽  
Anne Poli ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Advanced Ovarian Cancer ◽  
Standard Of Care ◽  
Maximum Tolerated Dose ◽  
Dependent Manner ◽  
Tyrosine Kinase 2 ◽  
Heavily Pretreated ◽  
Tumor Growth And Metastasis ◽  
Tumor Biopsies

TPS2620 Background: Blockade of FAK reduces tumor growth and metastasis through inhibition of tumor cell survival, proliferation and invasion as well as tumor angiogenesis. Furthermore, treatment with FAK inhibitors reduces the proportion of cancer stem cells (CSCs) in a dose dependent manner while paclitaxel treatment enriches for CSCs. (Kolev VN San Antonio Breast Cancer Symposia 2012 abstr P6-11-09). The ability of CSCs to survive exposure to chemotherapy but remain susceptible to novel drugs suggests a unique therapeutic approach whereby standard of care chemotherapy may be sequentially combined with targeted drugs to kill surviving CSCs and thus prevent tumor recurrence and metastasis. VS-6063 (previously PF-04554878) is a potent oral inhibitor of FAK and proline-rich tyrosine-kinase -2. The phase I first-in-man trial explored doses ranging from 12.5 -750 mg twice daily (BID). (Jones SF J Clin Oncol 2011 29:1 suppl; abstr 3002) Dose-limiting toxicities consisted of headache, fatigue, and unconjugated hyperbilirubinemia at various dose levels. A maximum tolerated dose was not defined, but doses > 100 mg BID consistently yielded concentrations above the preclinically predicted minimal efficacious concentration. Seven pts demonstrated stable disease lasting approximately 6 months or greater, including 3 heavily-pretreated ovarian cancer pts (2 platinum resistant). Methods: Pts with advanced or refractory ovarian cancer (≤ 4 prior regimens) will be enrolled. In the phase I portion, VS-6063 is administered continuously at a starting dose of 200mg BID with paclitaxel 80 mg/m2 on days 1, 8, and 15 every 28 days, and will be escalated to 400mg BID if tolerated. Pharmacokinetics will be analyzed. An additional 15 pts with biopsiable disease will be enrolled at the recommended dose. A 10-day run-in with VS-6063 alone will be used to obtain paired tumor biopsies in order to examine the effects on pFAK expression, CSCs, and other biomarkers. Patients will continue treatment until disease progression. Clinical trial information: NCT01778803.

Phase I Study of Fudr Continuous Infusion with Circadian Variability in Advanced Cancer Patients

1992 ◽  
Vol 78 (5) ◽  
pp. 341-344 ◽  
Author(s):  
Paolo Tralongo ◽  
Rosa Aiello ◽  
Francesco Ferraù ◽  
Orazio Marino ◽  
Francesco Cosentino ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Dose Intensity ◽  
Maximum Tolerated Dose ◽  
Entire Group ◽  
Low Grade ◽  
Advanced Cancer Patients ◽  
Starting Dose ◽  
Daily Dose ◽  
The Mean

A phase I study of floxuridine circadian infusion was performed in 14 patients with advanced solid tumors (9 colonic, 1 gastric, 4 renal). The starting dose was 0.15 mg/kg/day for 14 days followed by a 14-day therapy-free interval. Sixty-eight percent of the daily dose was infused between 3pm and 9pm. The dose was increased by 0.025 mg/kg/day for each successive course. Eighty-one cycles of therapy were given for a total of 1134 days of treatment. The mean dose intensity was 0.868 mg/kg/day for the entire group. The highest dose achieved (maximum tolerated dose) was 0.325 mg/kg/day. The most frequent toxicity was diarrhea (4.9 % of all courses) and nausea-vomiting (3.7 % of all courses). These side effects were of a low grade and all were resolved without hospitalization. Our results suggest the circadian modulation of floxuridine infusion.

Intraperitoneal carboplatin in icodextrin 4% as first-line treatment for epithelial ovarian cancer: A phase I/II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5522-5522
Author(s):  
L. Hofman ◽  
J. Sludden ◽  
A. V. Boddy ◽  
D. J. Murphy ◽  
D. R. Ferry
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Epithelial Ovarian Cancer ◽  
Maximum Tolerated Dose ◽  
Pharmacokinetic Data ◽  
Carrier Solution ◽  
First Line ◽  
Catheter Complications ◽  
The Mean ◽  
Dose Limiting Toxicity

5522 Background: First line intraperitoneal (IP) chemotherapy improves survival in epithelial ovarian cancer (EOC). Problems with IP delivery are not uncommon; in the GOG 172 study, 34% of patients discontinued IP therapy due to catheter complications. Icodextrin 4% is a high molecular weight solution for IP use, which produces a prolonged pharmacological ascites and reduces both post-surgical and post-chemotherapy adhesions. Methods: This phase I study investigated IP carboplatin in icodextrin 4% in optimally debulked EOC. Immediately post operatively, 1.5L Icodextrin 4% was infused IP. This was repeated on a weekly basis. Carboplatin was added 3-weekly, over 6 cycles. Carboplatin target AUC started at 5 mg/ml.min based on 51Cr EDTA clearance and the Calvert formula, and increased by increments of 1 mg/ml.min until dose limiting toxicity (DLT) was reached. Three to 6 patients were treated per dose level. IP fluid samples and blood samples were obtained immediately prior and after IP administration of carboplatin in icodextrin 4% and 1, 2, 4, 8, 12, 24, 48 h and 1 week after. Results: Fourteen patients were treated; 4 at AUC 5, 3 at AUC 6, 3 at AUC 7, 4 at AUC 8. DLT was reached at AUC 8. Myelosuppression was the DLT. The mean AUCs, measured in plasma ± SEM (and peritoneal fluid ± SEM), were: 5.8 ± 0.80 (55.2 ± 14.3), 4.9 ± 0.92 (43.0, 1 sample), 5.3 ± 1.3 (74.4 ± 25.3) and 7.5 ± 0.28 (135.3 ± 9.48) mg/ml.min for the target AUCs of 5, 6, 7 and 8 respectively. Two patients were withdrawn at the start of the 2nd cycle due to vaginal leaking of the IP installed icodextrin. The other 12 patients completed all 6 cycles without significant catheter problems or abdominal pain. Conclusions: The pharmacokinetic data suggest that carboplatin in icodextrin 4% is associated with a considerable IP pharmacokinetic advantage. Compared to data obtained on IP carboplatin in 5% glucose, icodextrin 4% does not seem to alter the pharmacokinetics of IP installed carboplatin. Icodextrin 4% appears to be an excellent carrier solution for IP carboplatin, with the potential to reduce catheter associated complications. To complete the phase II part of the study, 20 further patients will be treated at the maximum tolerated dose (MTD), AUC 7 mg/ml.min. No significant financial relationships to disclose.

scholarly journals A phase I study of combined trabectedin and pegylated liposomal doxorubicin therapy for advanced relapsed ovarian cancer

2021 ◽  
Author(s):  
Shunji Takahashi ◽  
Munetaka Takekuma ◽  
Kenji Tamura ◽  
Kazuhiro Takehara ◽  
Hiroyuki Nomura ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Phase I ◽  
Liposomal Doxorubicin ◽  
Advanced Ovarian Cancer ◽  
Pegylated Liposomal Doxorubicin ◽  
Japanese Patients ◽  
Pharmacokinetic Analysis ◽  
Dependent Manner ◽  
Drug Concentrations ◽  
Grade 3

Abstract Background Advanced relapsed ovarian cancer has a poor prognosis, and treatment options are limited. Methods This phase I trial investigated the dosage, safety, pharmacokinetics and efficacy of trabectedin plus pegylated liposomal doxorubicin (PLD) in Japanese patients with advanced relapsed ovarian, fallopian tube, or primary peritoneal cancer. Patients received trabectedin 0.9 or 1.1 mg/m2 immediately after PLD 30 mg/m2; both drugs were given by intravenous infusion. Treatment was repeated every 21 days until disease progression or unacceptable toxicity. The maximum tolerated dose (MTD) was determined in an initial dose escalation phase, and this was used in a subsequent safety assessment phase. Safety and tumor response were monitored throughout the trial, and drug concentrations for pharmacokinetic analysis were measured during cycle 1. Results Eighteen patients were included. The MTD of trabectedin was determined as 1.1 mg/m2. Gastrointestinal adverse events were experienced by all patients, but were mostly grade 1 or 2 in intensity. Most patients had grade ≥ 3 elevations in transaminase levels or grade ≥ 3 reductions in neutrophil count, but these events were generally manageable through dose reduction and/or supportive therapies, as appropriate. There were no deaths during the trial. Trabectedin exposure increased in a dose-dependent manner. The overall response rate was 27.8%. Conclusions Trabectedin, in combination with PLD, may have clinical benefits in Japanese patients with relapsed advanced ovarian cancer. The recommended dosage of trabectedin for further study in this population is 1.1 mg/m2 once every 21 days. Clinical trial registration number: JapicCTI-163164

Sign in / Sign up

Export Citation Format

Share Document