Intraperitoneal Carboplatin Research Articles

Antioxidant and anti-inflammatory activity by modulating IL-6 as a potential mechanism in the nephroprotective and hepatoprotective properties of Tribulus terrestris.

Carboplatin, a second-generation platinum-containing compound is associated with renal tubular injury and hepatic damage in cancer patients. Tribulus terrestris (TT) is widely used in Indian traditional medicine for its anti-inflammatory properties. The present study aimed to evaluate TT's beneficial effects against liver and kidney damage induced by carboplatin. An in-vivo study was conducted on thirty rats. All the groups, except the control, received intraperitoneal carboplatin 90 mg/kg on day 5; the three treatment groups received TT extract (1 g/kg, 1.25, and 1.5 g/kg) for 14 days. Serum and tissue parameters for liver functions, kidney functions, oxidative stress, and inflammatory marker interleukin 6 were measured along with histopathological assessment. TT at 1.5 g/kg on day 14 significantly reduced creatinine and aspartate transaminase levels compared to the carboplatin group. The increase in malondialdehyde levels and decrease in glutathione levels was significantly reversed in the groups treated with TT 1.25 and 1.5 g/kg. Interleukin 6 showed a significant decrease in treatment groups when compared to the carboplatin group. Carboplatin distorted hepatic architecture and caused diffused inflammatory cell infiltration in the peritubular interstitial spaces in the kidney. The histopathological evaluation confirmed that TT extract ameliorated hepatic and kidney damage by restoring to normal architecture. Aqueous extract of TT demonstrated a therapeutic effect against nephrotoxicity and hepatotoxicity caused by carboplatin. The observed benefits can be attributed to its anti-inflammatory action and antioxidant properties.

Prediction of response to promising first-line chemotherapy in ovarian cancer patients with residual peritoneal tumors: practical biomarkers and robust multiplex models.

Platinum/taxane (TC) chemotherapy with debulking surgery stays the mainstay of the treatment in ovarian cancer patients with peritoneal metastasis, and recently its novel modality, intraperitoneal carboplatin with dose-dense paclitaxel (ddTCip), was shown to have greater therapeutic impact. Nevertheless, the response varies among patients and consequent recurrence, or relapse often occurs. Discovery of therapeutic response predictor to ddTCip and/or TC therapy is eagerly awaited to improve the treatment outcome. Using datasets in 76 participants in our ddTCip study and published databases on patients received TC therapy, we first validated a total of 75 previously suggested markers, sought out more active biomarkers through the association analyses of genome-wide transcriptome and genotyping data with progression-free survival (PFS) and adverse events, and then developed multiplex statistical prediction models for PFS and toxicity by mainly using multiple regression analysis and the classification and regression tree (CART) algorithm. The association analyses revealed that SPINK1 could be a possible biomarker of ddTCip efficacy, while ABCB1 rs1045642 and ERCC1 rs11615 would be a predictor of hematologic toxicity and peripheral neuropathy, respectively. Multiple regression analyses and CART algorithm finally provided a potent efficacy prediction model using 5 gene expression data and robust multiplex toxicity prediction models-CART models using a total of 4 genotype combinations and multiple regression models using 15 polymorphisms on 12 genes. Biomarkers and multiplex models composed here could work well in the response prediction of ddTCip and/or TC therapy, which might contribute to realize optimal selection of the key therapy.

775P A gene expression signature to predict benefit from intraperitoneal (IP) carboplatin chemotherapy in ovarian carcinoma (OC): Translational research study from the intraperitoneal therapy for ovarian cancer with carboplatin (iPocc) phase II/III trial

775P A gene expression signature to predict benefit from intraperitoneal (IP) carboplatin chemotherapy in ovarian carcinoma (OC): Translational research study from the intraperitoneal therapy for ovarian cancer with carboplatin (iPocc) phase II/III trial

Intraperitoneal Carboplatin for Ovarian Cancer — A Phase 2/3 Trial

BackgroundIntraperitoneal chemotherapy has been shown to be effective at reducing mortality for patients with advanced epithelial ovarian cancer but is not widely used in practice.MethodsWe performed the Intraperitoneal Therapy for Ovarian Cancer with Carboplatin (iPocc) trial as an open-label, international, multi-institutional, randomized phase 2/3 clinical trial in women with newly diagnosed epithelial ovarian cancer who underwent laparotomy or laparoscopy. All patients received intravenous paclitaxel (80 mg/m2 on days 1, 8, and 15 of a 21-day cycle). In addition, patients in the control group received intravenous carboplatin (dose-dense intravenous paclitaxel plus intravenous carboplatin [dd-TCiv]), whereas patients in the experimental group received dose-dense intravenous paclitaxel plus intraperitoneal carboplatin (dd-TCip). The primary end point was progression-free survival (PFS). Secondary end points included overall survival, tumor response, treatment completion rate, and incidence of adverse events (AEs).ResultsAmong 655 patients randomized to treatment, median (95% confidence interval [CI]) PFS was 20.7 (18.1 to 22.8) months for dd-TCiv (n=328) and 23.5 (20.5 to 26.9) months for dd-TCip (n=327; hazard ratio, 0.83; 95% CI, 0.69 to 0.99; P=0.04). The PFS benefit with dd-TCip was consistent in patients with different baseline characteristics, stage, size of residual tumor, age, and performance status. The treatment completion rates were 68.3 and 59.9% in the dd-TCiv and dd-TCip groups, respectively. The incidence of intraperitoneal catheter-related AEs in the dd-TCip group was 10.1%; there were no such AEs in the dd-TCiv group.ConclusionsIn the first-line treatment of advanced epithelial ovarian cancer, intraperitoneal carboplatin resulted in a modest prolongation of PFS when given with dose-dense weekly paclitaxel regardless of residual tumor size, with no impact on noncatheter-related toxicities. (Funded by the Japan Agency for Medical Research and Development, and others; Japan Registry of Clinical Trials number, jRCTs031180141.)

577P Impact of homologous recombination deficiency (HRD) on outcomes with intraperitoneal (IP) and intravenous (IV) chemotherapy in ovarian cancer: Analyses from the translational iPocc study (TriPocc)

The iPocc randomised multicentre international study reported improved progression-free survival (PFS) but not overall survival (OS) with IP carboplatin and IV paclitaxel vs IV chemotherapy (chemo) in patients (pts) with epithelial ovarian, fallopian tube or primary peritoneal cancer. Previous studies suggested that pts with BRCA-deficient tumours may benefit from IP chemo. We conducted a non-prespecified analysis of the prognostic and predictive value of HRD in tissue samples retrospectively obtained from iPocc trial pts.

A randomized phase 3 trial of intraperitoneal versus intravenous carboplatin with dose-dense weekly paclitaxel in patients with ovarian, fallopian tube, or primary peritoneal carcinoma (a GOTIC-001/JGOG-3019/GCIG, iPocc Trial) (LBA 3)

<b>Objectives:</b> Traditionally, the target of intraperitoneal (IP) chemotherapy for ovarian cancer was patients with minimal residual disease after debulking surgery. However, our pharmacological study suggested that IP carboplatin therapy should also be feasible for patients with larger size residual disease, and our previous phase 2 study demonstrated a satisfactory response rate of IP carboplatin plus dose-dense paclitaxel (ddTCip) regimen in patients with macroscopic residual disease after initial surgery for ovarian (OV), fallopian tube (FT), and primary peritoneal (PP) carcinoma. The purpose of this study is to assess whether IP administration of carboplatin is superior to intravenous (IV) administration of carboplatin (ddTCiv regimen) in OV, FT, and PP carcinoma patients with either minimal or macroscopic residual disease. <b>Methods:</b> Eligible patients were those with newly diagnosed stages II-IV disease. All patients were to undergo an initial laparotomy or laparoscopy with primary debulking surgery if possible. Before abdomen was closed, patients were randomized to either IV or IP arm. An IP port and catheter was placed if the patient was assigned to IP arm. Chemotherapy regimen was either IV paclitaxel plus IV carboplatin (IV arm) or IV paclitaxel plus IP carboplatin (IP arm). Dose of paclitaxel was 80 mg/m² Q1W and dose of carboplatin was at an area under the curve (AUC) of 6 Q3W. Each patient was to receive 6 to 8 cycles of chemotherapy. Patients with bulky residual disease were allowed to undergo interval debulking surgery followed by assigned arm regimen up to 8 cycles total. Primary endpoint was PFS, and secondary endpoints included OS, safety, QOL, and cost/benefit. <b>Results:</b> Total of 655 patients were randomized between 2010 and 2016 from Japan, Singapore, Korea, New Zealand, USA, and Hong Kong. Stage distribution was II (n= 88), III (n=448), and IV (n=119). Size of residual disease at randomization was either 0 cm (n=163), < 1 cm (n=97), 1-2 cm (n=33), or >2 cm (n=362). Histological types were serous (n=420), endometrioid (n=61), clear cell (n=74), and others (n=100). Median follow-up was 55.7 months. IP chemotherapy significantly improved PFS in the ITT population (HR=0.83, 95%CI:0.69-0.99, p=.041) and in the 602 eligible patients (HR=0.78, 95%CI:0.65-0.94, p=.009). Median PFS for ITT population was 20.7 (95%CI: 18.1-22.8) months in the IV arm and 23.5 (95%CI: 20.5-26.9) months in the IP arm. Median PFS for eligible patients was 20.0 (95%CI: 18.0-22.2) months in the IV arm and 22.9 (95%CI:19.6-26.9) months in the IP arm. Subset analysis showed that the survival benefit was greater in patients with larger size residual disease. Toxicity profile was essentially equivalent in both arms except for catheter-related toxicities (11.8%). <b>Conclusions:</b> ddTCip chemotherapy improved the PFS over ddTCiv regimen in patients with OV, FT, and PP carcinoma regardless of the residual tumor size after initial surgery.

2-Pyrocatechuic Acid Attenuates Carboplatin Induced Hematological Toxicities in Wistar Rats

Hematological toxicity or pancytopenia produced by carboplatin chemotherapy tends to limit the clinical usage of carboplatin as a potent antineoplastic agent. The current investigation was aimed at evaluation of the protective activity of a plant phenolic acid i.e. 2-pyrocatechuic acid (2,3 dihyroxybenzoic acid) against hematological adverse effects induced by carboplatin in Wistar rats. Intraperitoneal injection carboplatin (35 mg/kg) for 6 days resulted in significant alterations in hematological parameters such as decreased red blood cell, hemoglobin, total leukocyte and differential leukocyte counts and increased eosinophil counts in rat blood indicating severe hematological toxicities. Pre and co-administration of 2-pyrocatechuic acid at the doses 10, 30 and 100 with CP significantly attenuated the altered hematological indices in a dose-dependent manner exhibiting its efficacy as a protective agent for the amelioration and prevention of hematological toxicities induced by carboplatin chemotherapy.

History of intraperitoneal platinum drug delivery for ovarian cancer and its future applications

Intraperitoneal (IP) delivery of cisplatin was developed in the 1970s based on a strong pharmacologic rationale and rodent models. Its advantage over intravenous (IV) administration was supported initially by observational studies in treating recurrent ovarian cancer and eventually by better outcomes from IP vs. IV cisplatin in randomized studies in patients undergoing optimal surgical debulking at diagnosis. In the past two decades, with the introduction of novel anticancer interventions (such as taxanes, bevacizumab, inhibitors of DNA repair, and immune check point inhibitors), advantages of IP drug delivery are less clear and concerns are raised on cisplatin's therapeutic index. The discovery of BRCA genes and their key role in DNA repair, on the other hand, have strengthened the rationale for IP drug delivery: high grade serous cancers arising in the Mullerian epithelium in association with hereditary or somatic BRCA function inactivation are linked to peritoneal spread of cells that - while initially sensitive - are prone to emergence of platinum resistance. Therefore, selection of patients based on genomic features and focusing on the better tolerated IP carboplatin are ongoing. Recent examples of leveraging the peritoneal route include (1) targeting the cell membrane copper transport receptor - that is shared by platinums - by the combination of the proteasome inhibitor bortezomib and IP carboplatin; and (2) enhancing IP 5-fluoro-2-deoxyuridine cytotoxicity when coupled with PARP inhibition.

Phase II Trial on the Feasibility of Single-Dose Intraoperative Intraperitoneal Carboplatin in Advanced Epithelial Ovarian Cancer Following Optimal Cytoreductive Surgery.

To evaluate the feasibility administering single-dose intraoperative intraperitoneal carboplatin (IP) in advanced epithelial ovarian cancer (EOC) after optimal primary or interval debulking surgery. A phase II non-randomized prospective study conducted at a regional cancer institute from January 2015 to December 2019. The advanced high-grade epithelial ovarian cancer FIGO stage IIIB-IVA was included. A total of 86 consented patients with optimal primary and interval cytoreductive surgeries received single-dose intraoperative IP carboplatin. The immediate (< 6h), early (6-48h), and late (48h-21days) perioperative complications were recorded and analyzed. The severity of adverse events was graded on the basis of National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). A total of 86 patients received single-dose intra-operative IP carboplatin during the study period. The 12 (14%) patients underwent primary debulking surgery and 74(86%) interval debulking surgery (IDS). The 13 (15.1%) patients underwent laparoscopic/robotic IDS. All the patients tolerated the intraperitoneal carboplatin well with no or minimal adverse events. Three cases (3.5%) needed resuturing for the burst abdomen, three cases (3.5%) had paralytic ileus for 3-4days, one case (1.2%) underwent re-explorative laparotomy for hemorrhage, and one case (1.2%) mortality due to due late sepsis. The 84 (97.7%) of 86 cases received scheduled IV chemotherapy on time. Single-dose intraoperative IP carboplatin is a feasible procedure with no or minimal manageable morbidity. The procedure is user friendly combining the prognostic benefits of IP chemotherapy with assurance of earliest timely administration of chemotherapy in advanced EOC. Our study is a hypothesis generating for the future clinical trials comparing single-dose NIPEC versus HIPEC in advanced EOC.

A phase 2 study of intraperitoneal carboplatin plus intravenous dose-dense paclitaxel in front-line treatment of suboptimal residual ovarian cancer

BackgroundWe evaluated the efficacy of intraperitoneal (IP) carboplatin in combination with dose-dense paclitaxel (ddTCip) for suboptimal residual ovarian cancer.MethodsThis was a phase 2 study to evaluate ddTCip. Patients with stage II–IV ovarian carcinoma, who underwent primary cytoreductive surgery and had radiologically evaluable disease after surgery, were eligible to participate in this study. IP carboplatin (AUC = 6) was administered on day 1, and intravenous paclitaxel (80 mg/m2) was administered on days 1, 8 and 15. The primary endpoint was response rate. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. Interval- debulking surgery followed by the same regimen was allowed when indicated.ResultsA total of 117 patients were considered eligible for this study prior to surgery and temporarily registered. Of the 117 patients, 76 patients met the inclusion criteria and were enrolled in this study. Fifty-nine (83.1%) patients had objective clinical responses. Median PFS and OS were 18.3 and 55.5 months, respectively. Sixty-four (84.2%) patients had grade 3/4 neutropenia, 43 (56.5%) patients had anaemia and 17 (22.4%) patients had thrombocytopenia. Port-related adverse events occurred in nine (11.8%) patients.ConclusionsFront-line chemotherapy with ddTCip therapy appears safe and effective, even for patients with suboptimal residual ovarian cancer.Trial registrationUMIN Clinical Trials Registry (ID: UMIN000001713) on February 16th, 2009.

Treatment Tolerance and Side Effects of Intraperitoneal Carboplatin and Dose-Dense Intravenous Paclitaxel in Ovarian Cancer.

To describe the frequency of clinically significant side effects associated with adjuvant intraperitoneal (IP) carboplatin and intravenous (IV) dose-dense paclitaxel chemotherapy for epithelial ovarian cancer (EOC). Patients with stage II to IV EOC who underwent upfront cytoreductive surgery followed by adjuvant IP carboplatin (AUC 6) every 3 weeks with IV paclitaxel weekly at 80 mg/m2 were included. Side effects and the resulting changes in treatment are presented using univariate analysis and compared to major phase III RCTs. Between March 2013 and October 2015, 49 patients comprising 289 cycles of chemotherapy were included in the analysis; 43 patients (87.8%) completed six cycles of chemotherapy and 38 (77.6%) completed six cycles of IP carboplatin. Treatment was discontinued early due to neuropathy (5/49) and disease progression (1/49). Carboplatin IV was substituted due to port access (3/49) and poor postoperative performance status (3/49). Neutropenia occurred in 16 patients (32.7%). Fourteen patients (28.6%) required red blood cell transfusion. Thrombocytopenia affected nine patients (18.4%). Infection delaying treatment occurred in five patients (10.4%). Gastrointestinal and renal toxicity occurred in four (8.1%) and one patient (2.0%), respectively. Four patients experienced a taxane reaction. No patients experienced ototoxicity, fistula formation, chemotherapy leakage, or severe abdominal pain. Carboplatin IP and weekly IV paclitaxel was well-tolerated with a side-effect profile similar to or better than previously published traditional treatment regimens.

Long-term survival after intraperitoneal carboplatin chemotherapy for advanced ovarian cancer

Objective: Multiple RCTs show increased overall survival in women with advanced ovarian cancer treated with intraperitoneal (IP) cisplatin chemotherapy compared to intravenous; however, uptake is poor because of toxicity concerns. Substitution of IP carboplatin as a viable therapeutic option was analyzed for outcomes.

Integrated molecular analysis of Asian ovarian cancer: Gene expression and whole exome sequencing analyses from the iPocc Translational Research study (TriPocc).

5562 Background: iPocc is a randomized, multicenter international study comparing the efficacy of first line intravenous (IV) dose-dense paclitaxel and intraperitoneal (IP) carboplatin with standard IV dose-dense paclitaxel and carboplatin in women with epithelial ovarian, fallopian tube or primary peritoneal cancer. TriPocc is the translational research protocol evaluating the molecular and predictive biomarkers for differences in treatment outcome. Methods: Fresh frozen (FF) biopsies (N = 123) collected during surgeries from participating institutions in Japan and Singapore were included into TriPocc. Briefly, DNA and RNA were extracted from FF biopsies and paired germline DNA were extracted from the peripheral blood mononuclear cells (PBMC). Whole-transcriptome profiling (WTP) was done by Affymetrix Human Transcriptome Array (HTA) 2.0 (N = 120) for gene expression molecular subtypes (GEMS). Whole-exome sequencing (WES) was done by Nextera Rapid Capture Custom Enrichment Kit for library preparation followed by Illumina NextSeq 500 for paired somatic and germline sequencing (N = 116). The Broad Institute Genome Analysis Tool Kit (GATK) V3.7 was used for variant calling. Results: High grade serous carcinoma (HGSC) was the most frequent histotype (N = 72; 60%), followed by endometrioid (N = 18; 15%) and clear cell carcinoma (N = 16; 13.3%). Mes was the dominant GEMS (N = 43; 35.8%), followed by Epi-B (N = 29; 24.2%), Stem-A (N = 27; 22.5%), Stem-B (N = 17; 14.2%), and Epi-A (N = 4; 3.3%). Unique mutations were discovered in HGSC. Top significant mutations identified (q-value lower than 1xE-9) included ITGA4, UCN3, COL4A3, ACP2, SEH1L, AGL, FAM26F, OR5H15, EXO1, TEKT3, ZNF720, IFI44L, MERTK, TP53, DHX57, TTC31, which were not reported previously in the TCGA cohort. BRCA1/2 mutations (26.1% of all samples) were found in 35.2% of HGSC and 13.5% of non-HGSC, which is higher than previously reported. Conclusions: The integrated genomic analysis from TriPocc has enabled the discovery of potentially novel molecular alterations in Asian ovarian cancers. The predictive value of these molecular alterations will be assessed once the iPocc outcome data are mature.

The Role of Intraperitoneal Carboplatin as Consalidation Chemotherapy in Women with Ovarian Carcinoma: Report of Our Experience and Systematic Review

Background: Epithelial ovarian cancer is the leading cause of death from gynecology malignancy. The aim of this study was to assess the role of intraperitoneal chemotherapy with carboplatin, as a consolidative treatment, in reducing relapse and increasing survival of patients in advanced epithelial ovarian cancers, as well as evaluation of its toxicity. Methods: This clinical trial was conducted on 30 patients with epithelial ovarian cancer in stages II-IV in Gynecology oncology department in Valiasr University Hospital, Tehran during 2005-2010. They were enrolled through non-random sequential selection. They divided into 18 cases as the intervention group (receiving intraperitoneal chemotherapy) and 12 patients as the control group (with only retrospective follow-up). The cases received 3 cycles of 400 mg/m2 intraperitoneal carboplatin every 21 days following intravenous chemotherapy. Mean survival of two and five years, progression-free interval, overall survival, relapse, demographic parameters, drug toxicities and pathologic types of cancers were coded in the two groups and compared using SPSS 14. Results: The mean ages of cases and controls were 52.4 ± 8.6 and 55.1 ± 11.5 years. The mean duration of relapse-free survival was 13 ± 8.6 months for the cases and 9.5 ± 4.3 months for the control patients (not statistically different, P&gt;0.05). The mean overall survival for cases and controls were 39 ± 16.5 and 30.8 ± 16.2 months, respectively (no significant difference, P&gt;0.05). The frequency of drug toxicities in the cases was 5.6%, and consisted of mild-to-moderate abdominal pain, nausea and vomiting. Conclusion: consolidation therapy with intraperitoneal carboplatin may not increase overall survival, reduce relapse rate or decrease mortality, though it does not induce considerable side effects.

OV21/PETROC: A randomized Gynecologic Cancer Intergroup (GCIG) phase II study of intraperitoneal (IP) versus intravenous (IV) chemotherapy following neoadjuvant chemotherapy and optimal debulking surgery in epithelial ovarian cancer (EOC).

LBA5503 Background: The aim of this 2 stage randomized trial was to evaluate whether women undergoing neoadjuvant IV chemotherapy followed by delayed debulking surgery benefit from the addition of IP/IV treatment after surgery. Methods: Stage 1 was a randomized 3-arm design including 2 IP platinum regimens: 153 women who received 3-4 courses of IV platinum-based chemo for stage IIB-III (IV pleural effusion only) EOC followed by optimal debulking surgery ( &lt; 1 cm) were randomized to: ARM1 D1 IV paclitaxel (pacli) 135mg/m2 + IV Carboplatin AUC 5/6 with d8 pacli IV 60 mg/m2 Q 21d X3; ARM 2 D1 IV pacli 135mg/m2 + IP cisplatin (Cis) 75 mg/m2 and d8 IP pacli 60 mg/m2 Q21d X3; or ARM 3 d1 IV pacli 135mg/m2+ IP Carboplatin AUC 5/6 and d8 IP pacli 60mg/m2 Q21dX3. A planned DSMC review confirmed dropping ARM2 (IP cis) and continuing study as an expanded phase II comparing 200 patients randomized to ARMs 1 and 3, which has 80% power to detect a 19% difference in progression rate at 9 mo (PD9, primary endpoint), 2-sided α = 0.05. Progression free survival (PFS) and overall survival (OS) are secondary efficacy endpoints. Results: Between 2009 and May 2015, 275 patients were accrued: n = 101 Arm 1, 72 Arm 2, 102 Arm 3. Median age was 62; 81.8%s had stage 3 C disease; 12.7% stage IV. Baseline characteristics were balanced between arms. Median number of cycles was 3 all arms; completion rates Arm 1, 93.7% and Arm 3, 84.8%. Intention to treat PD9 rates: Arm 1: 38.6% (95% CI 29.1%- 48.8%) and Arm 3: 24.5% (95% CI 16.5%-34.0%); p = 0.065 stratified; p = 0.03 unstratified. Per protocol (eligible, received &gt; one dose of protocol therapy) PD9 rates: Arm 1: 42.2% (95% CI 31.9%- 53.1%), Arm 3: 23.3% (95% CI 15.1%-33.4%); p = 0.03 stratified; p = 0.01 unstratified. Median PFS 11.3 mo (Arm1) and 12.5 mo (Arm 3); HR 0.82 (95% CI 0.57 - 1.17); p = 0.27. Median OS: 38.1 mo (Arm 1) and 59.3 mo (Arm 3); HR 0.80 (95% CI 0.47-1.35) p = 0.40. Adverse events &gt; Gr 3 rates: 23% (Arm 1) and 16% (Arm 3) (p = 0.24). Conclusions: The IP carboplatin based regimen, post neoadjuvant chemotherapy and debulking surgery, is well tolerated and associated with a lower PD9 rate compared to IV therapy. Clinical trial information: NCT00993655.

267PD Survival, clinical activity and safety of intraperitoneal carboplatin combined with intravenous dose-dense paclitaxel in patients with ovarian carcinoma: a retrospective study of 69 cases

267PD Survival, clinical activity and safety of intraperitoneal carboplatin combined with intravenous dose-dense paclitaxel in patients with ovarian carcinoma: a retrospective study of 69 cases

A comparison of the toxicity and tolerability of two intraperitoneal chemotherapy regimens for advanced-stage epithelial ovarian cancer

ObjectivesRandomized controlled trials (RCTs) in optimally cytoreduced epithelial ovarian cancer (EOC) patients have demonstrated an impressive survival benefit of intraperitoneal (IP) platinum over intravenous (IV), but its use has been limited by significant toxicity from cisplatin. The aim of this study was to compare the toxicity and tolerability of IP cisplatin to IP carboplatin in women with optimally cytoreduced EOC. MethodsRetrospective analysis of 141 women with EOC who underwent optimal surgical cytoreduction followed by IV paclitaxel and IP cisplatin or IP carboplatin was performed. Toxicities of the two treatment regimens were compared. As a secondary outcome, overall survival (OS) and progression-free survival (PFS) probabilities were obtained using the Kaplan–Meier estimate; the log-rank test was used to compare survival curves. ResultsOf the 141 patients, 77 (54.6%) received IP cisplatin and 64 (45.4%) received IP carboplatin. Eighty-six percent received at least 4cycles of IP chemotherapy. IP cisplatin was associated with significantly more grade 3 nausea and vomiting (10.4% vs 1.6%, p=0.033), grade 3 neuropathy (7.8% vs 0%, p=0.013) and grade 2–3 neutropenia (22.1% vs 9.4%, p=0.042). No difference in PFS (p=0.602) or OS (p=0.107) was found between the groups. ConclusionIP chemotherapy had a high completion rate in both groups of patients. IP carboplatin required a less resource intense protocol and was tolerated better than IP cisplatin with less gastrointestinal, neurologic and hematologic toxicities.

Results of a phase I pharmacokinetic study of intraperitoneal bortezomib (B) and carboplatin (C) in patients with persistent or recurrent ovarian cancer (OC): An NRG/Gynecologic Oncology Group study.

5515 Background: Intraperitoneal therapy (IP) has been shown to improve survival outcomes for women with optimally cytoreduced, newly diagnosed, advanced OC, but whether IP has a role for recurrent...

Atypical presentation of a schwannoma mimicking recurrence of primary peritoneal cancer

In August 2013, a woman aged 59 years with known stage IIIC primary peritoneal cancer underwent robotic hysterectomy, bilateral salpingo-oophorectomy, lymph node dissection, omentectomy, and optimal debulking. She did not smoke and had never been pregnant. Her medical history included asthma, nephrolithiasis, heart murmur, and diethylstilbestrol exposure in utero. She had completed her sixth cycle of intravenous and intraperitoneal carboplatin and paclitaxel. She planned on joining the GOG212 study (NCT00108745), which is a randomized phase 3 trial comparing paclitaxel, polyglutamate paclitaxel, and observation only in patients with stage III or stage IV ovarian epithelial, peritoneal, or fallopian tube cancer. During work-up for the study, a restaging computed tomography (CT) scan on January 7, 2014, revealed a 3-cm left iliac retroperitoneal mass, suspicious for recurrent cancer in an enlarged lymph node. The mass had not been identified on a CT scan performed 3 weeks before her initial surgery. Cancer antigen 125 levels were within normal range. The patient underwent an uncomplicated robotic-assisted laparoscopic resection of the retroperitoneal mass and left pelvic lymph node dissection; cryosection was performed to rule out persistent disease. Intraoperative evaluation of the mass revealed a low-grade spindle cell tumor. Evaluation of a permanent section revealed that the mass was S100 positive, and actin and desmin negative—findings consistent with schwannoma. The remaining peritoneal biopsy samples were negative. After surgery, she developed neuropathy of the left lower leg, with weakness on hip flexion, and intermittent numbness of the left foot. She could walk without difficulty. The deficit improved slowly, and the patient declined physical therapy. As of January 2015, there were no residual symptoms remaining. The findings of the surgery were discussed with the patient. The GOG212 study was no longer recruiting patients at this point, so maintenance chemotherapy with paclitaxel was resumed. The patient provided informed consent for publication of the present report. Retroperitoneal schwannomas are uncommon, but have been reported in the literature. The point of interest in the case reported here is the nature of the tumor, mimicking a recurrence of the patient’s cancer. The patient was on chemotherapy during the time of diagnosis, usually indicating recurrence with metastases. Two cases of retroperitoneal schwannomas mimicking metastatic seminomas have been previously reported [1,2]. Both were treated with chemotherapy, without a response. Excision of the lesions revealed a pathologic diagnosis of benign schwannoma requiring no further treatment. Schwannomas are difficult to diagnose without surgical evaluation, but should be considered in the differential diagnosis when a mass is not responsive to chemotherapy. A misdiagnosis could potentially cause overtreatment and unnecessary adverse effects.

Ovarian clear cell carcinoma comprising dual components of differential alpha-fetoprotein productivity and drug sensitivity

Epithelial ovarian tumor with elevated alpha-fetoprotein (AFP) is extremely rare and eventually needs differential diagnosis. This study investigated AFP-producing ovarian pure clear cell carcinoma without any components differentiating it to yolk sac tumor or hepatoid carcinoma. A 51-year-old Japanese woman presented with lower-abdominal distension continued for 6 months and was found to have a huge lower-abdominal mass on pelvic examination and MRI scan. Laboratory tests showed serum AFP 31533 ng/ml, CA125 456 U/ml, and LDH 485 IU/l. Bilateral salpingo-oophorectomy, total hysterectomy and omentectomy were performed with <1 cm residual macroscopic tumor. Microscopically, the tumor was characterized by typical clear cell carcinoma without any differentiating components. Pathologic stage was pT3cNxM0. Tumor cells were diffusely immunoreactive for AFP with more prominent staining on cell block cytology from ascites than surgical specimen. The patient was treated by 6 cycles of chemotherapy composed of dose-dense paclitaxel with intraperitoneal carboplatin, producing normalization of both AFP and CA125 without any evidence of the disease. After 11 months, she showed remarkable increase in CA125 to 1365 u/ml, with normal level of AFP. The recurrent tumor was resected and she received chemotherapy with gemcitabine and carboplatin, producing stabilization of the disease without any fluctuations in CA125 level. Eight months after, she showed slight increase of AFP to 29 ng/ml with uncontrollable massive ascites which was out of control resulting in her death.