Correlative study of low serum creatinine and hematological toxicities in Japanese patients with ovarian cancer treated by dose dense TC therapy.

5045 Background: Dose dense TC (ddTC) is a novel standard therapy for patients (pts) with advanced ovarian cancer, although hematological toxicities (hemTX), especially anemia, may increase as observed in NOVEL trial (JGOG3016). Low serum creatinine (LCr), especially below 0.7 mg/dl, may lead to overestimation of GFR. GOG announced that pts with LCr should use a minimum value of 0.7mg/dl to estimate GFR. The correlation between LCr and hemTX treated by ddTC is unknown. Methods: GFR was determined using the Cockcroft-Gault formula. Serum creatinine concentrations were measured using enzymatic assays. Minimum value of 0.7 mg/dl was not used during this period of time. The carboplatin clearance was then calculated by Calvert equation. HemTX were defined as, Grade 3 or 4 (by CTC-AE ver.4) neutropenia, anemia, and thrombocytopenia. Using electrical chart, frequency of hemTX and correlation between serum creatinine (less than 0.7 or not) were examined. Results: From Feb. 2010 to Dec. 2011, 61 consecutive pts were treated with ddTC. LCr was observed in 73% of pts. No treatment related death occurred. Among 61 pts, 50 (82%), 31 (51%), and 12 (19.6 %) pts experienced Grade3/4 neutropenia, anemia and thrombocytopenia, respectively. HemTX in pts with LCr and the others were as in the Table. Conclusions: LCr is frequent in Japanese female pts. ddTC in practice setting seems safe, and hemTX of ddTC are similar with those observed in NOVEL trial. The rationale using a minimum value of 0.7 mg/dl should be further studied by larger population, such as pts in NOVEL trial. [Table: see text]

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Correlative Study of Low Serum Creatinine and Hematological Toxic Effects in Japanese Patients with Ovarian Cancer Treated by Dose Dense TC Therapy

Annals of Oncology ◽

10.1016/s0923-7534(20)32356-5 ◽

2012 ◽

Vol 23 ◽

pp. xi125-xi126

Author(s):

K. Matsumoto ◽

T. Onoe ◽

A. Kitao ◽

M. Tanioka ◽

S. Negoro

Keyword(s):

Ovarian Cancer ◽

Serum Creatinine ◽

Japanese Patients ◽

Toxic Effects ◽

Correlative Study ◽

Dose Dense ◽

Low Serum

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

International Journal of Clinical Oncology ◽

10.1007/s10147-021-01973-1 ◽

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

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The Prognostic Impact of the Pathological Response to Neoadjuvant Dose-Dense Therapy for Ovarian Carcinoma

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001107 ◽

2017 ◽

Vol 27 (9) ◽

pp. 1850-1855 ◽

Cited By ~ 4

Author(s):

Takahiro Ebata ◽

Mayu Yunokawa ◽

Hiroshi Yoshida ◽

Seiko Bun ◽

Tatsunori Shimoi ◽

...

Keyword(s):

Ovarian Cancer ◽

Prognostic Factors ◽

Tumor Cells ◽

Advanced Ovarian Cancer ◽

Progression Free Survival ◽

Complete Response ◽

Pathological Response ◽

Prognostic Impact ◽

Grade 3 ◽

Dose Dense

ObjectiveThe aim of this study was to assess the use of the pathological response to neoadjuvant chemotherapy (NAC) for predicting disease prognosis in patients with advanced ovarian cancer who received neoadjuvant dose-dense weekly paclitaxel and carboplatin (dd-TC) therapy.MethodsWe retrospectively investigated patients with advanced epithelial ovarian, tubal, or peritoneal carcinoma treated at our hospital from July 2004 to October 2014. Patients received dd-TC therapy as NAC followed by interval debulking surgery (IDS). Specimens resected during IDS were divided into 4 groups based on pathological response: grade 1, most tumor cells appeared to be viable; grade 2a, most tumor cells had disappeared, whereas the remaining tumor cells were vacuolated or degenerated; grade 2b, small numbers of viable tumor cells were observed; and grade 3, small aggregations of macrophages were seen.ResultsSixty-eight patients were enrolled. The median number of NAC cycles was 3 (range, 2–6), and 51 patients (75.0%) achieved complete resection at IDS. Regarding pathological response, 7 (10.3%) patients were classified as grade 1, 11 (16.2%) as grade 2a, 46 (67.7%) as grade 2b, and 4 (5.9%) as grade 3. In univariate and multivariate analyses, grades 2b and 3 pathological responses were significant favorable prognostic factors for progression-free survival (P = 0.028; hazard ratio, 0.48; 95% confidence interval, 0.26–0.92).ConclusionsAlthough the pathological complete response rate to NAC was low in this study, both complete and good pathological responses to NAC might be favorable prognostic factors for PFS in patients with advanced ovarian cancer who receive dd-TC.

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Dose-dense early postoperative intraperitoneal chemotherapy in ovarian cancer: Randomized, phase II trial.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.5514 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 5514-5514

Author(s):

Rongyu Zang ◽

Tingyan Shi ◽

Rong Jiang ◽

Hong Pu ◽

Huijuan Yang ◽

...

Keyword(s):

Ovarian Cancer ◽

Residual Disease ◽

Advanced Ovarian Cancer ◽

Wild Type ◽

Phase 2 Trial ◽

Randomized Phase Ii ◽

Grade 3 ◽

Dose Dense ◽

Optimal Debulking ◽

A Prospective Study

5514 Background: Dose-dense early postoperative intraperitoneal chemo (DD-EPIC) had been carried out in advanced ovarian cancer (OC) pts in China over the past three decades but it was not proved by a prospective study. This trial was designed to confirm the benefit of DD-EPIC in delaying progression and improving survival. Methods: In a multicenter, phase 2 trial, pts with FIGO IIIC-IV OC and optimal debulking surgery (residual disease ≤1cm) were randomly allocated to receive 4 doses of weekly DD-EPIC with cisplatin (50mg/m2) and etoposide (100mg/m2) followed by 6 cycles of intravenous (iv) chemo with carboplatin and taxane every 3 weeks (DD-EPIC group), or standard iv chemo alone (iv group). (ClinicalTrials.gov, NCT01669226). Results: Between 2009 and 2015, 218 pts were randomized, of whom 215 initiated treatment (106 to DD-EPIC and 109 to iv; for efficacy analyses). Totally, 36 pts (16·7%) were received neoadjuvant chemo. With a median of 61·9 mos follow-up, 122 pts died (54 in DD-EPIC and 68 in iv group). Remarkable OS benefit of DD-EPIC was recorded (67·5 mos for DD-EPIC vs. 46·3 mos for iv; HR 0·70, 95% CI 0·49-1·00, P=0·047). Pts in DD-EPIC had a significantly increased median PFS compared with those in iv group (21·7 vs. 16·8 mos; HR 0·64, 95% CI 0·47-0·86, P=0·003). Median TFST was 25·1 vs. 18·0 mos in favor of DD-EPIC (HR 0·62, 95%CI 0·46-0·83, P=0·002). Similar findings were detected in TSST (42·2 vs. 29·3 mos; HR 0·66, 95%CI 0·47-0·94, P=0·019). Grade 3 and 4 Leucopenia (53·8% vs. 35·2%), anemia (23·6% vs. 5·6%) and gastrointestinal events (10·4% vs. 1·9%) were more common in DD-EPIC ( P=0·006, P<0·001 and P=0·010, respectively). Ninety-one pts were detected by gBRCA testing, with 25·3% of cases carrying deleterious BRCAm, but PFS and OS benefit were observed in patients with BRCA-wild type (HR 0·46 and 0·55, 95%CI 0·27-0·81 and 0·27-1·11, respectively). Conclusions: DD-EPIC with a higher completion rate and acceptable treatment burden was associated with longer OS than standard iv alone. Owing to the benefit of relatively long-term OS, DD-EPIC may be considered as a valuable option for OC, particularly in developing countries and BRCA-wild type pts. Clinical trial information: NCT01669226. [Table: see text]

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