Carboplatin Combination Chemotherapy Research Articles

O3-3-1 - A Phase II Study of Amrubicin and Carboplatin for Untreated Patients with Extensive-Diasese Small Cell Lung Cancer

Background: Amrubicin is active in the treatment ofextensive-disease small cell lung cancer (ED-SCLC), and carboplatin is an analogue of cisplatin with less non-hematological toxicity.Purpose: To determine the efficacy and toxicity ofamrubicin and carboplatin combination chemotherapy for previously untreated patients with ED-SCLC.Patients and methods: Eligibility criteria were chemotherapy-naive ED-SCLC patients, performance status 0-1, age< 75, and adequate hematological, hepatic and renal function. Based on the phase I study, the patients received amrubic in 35 mg/m2 i.v. infusion on days 1,2 and 3, and carboplatin AUC 5 i.v. infusion on day 1. Four cycles of chemotherapy were repeated every 3 weeks.Results: Thirty-five patients were enrolled and 34 patients were eligible and assessable for response, toxicity and survival.Patients' characteristics are as follows: male/female = 26/8; performance status (PS) 0/1 = 4/30; median age (range) = 64 (41-75); stage IV = 34. Evaluation of responses were 6 complete response (CR), 21 partial response (PR), and 7 stable disease (SD) (response rate 79.4%, 95%CI 63.6-88.5%). Grade 3 and 4 leukopenia, neutropenia, and thrombocytopenia occurred in 59%, 82%, and 26%, respectively. There were no treatment-related deaths or pneumonitis. Three patients experienced hypotension as an amrubicin infusion reaction. The median progression-free survival time was 6.5 months. The median overall survival time and 1-, 2- and 3-year survival rates were 15.6 months, 63%, 28% and 7%, respectively.Conclusions: Amrubicin and carboplatin was effective and tolerable as chemotherapy for previously untreated patients with ED-SCLC. Further investigation of amrubicin and carboplatin is warranted.

Abstract 2821: Dual-label microdosing approach to identify chemoresistance to carboplatin and gemcitabine combination chemotherapy

Abstract Gemcitabine is commonly given in combination with cisplatin or carboplatin (GC therapy) as the first-line chemotherapy regimen for several malignancies, including bladder cancer. Unfortunately, less than half of patients respond to the therapy, generating a critical need for a test that predicts tumor response to GC therapy. The goal of this project is to measure drug-DNA adducts after administration of a single non-toxic microdose of gemcitabine in combination with carboplatin and correlating the degree of modification to chemotherapy sensitivity. We have previously shown that resistance to carboplatin may be identified by using a [14C]carboplatin microdose (1% of therapeutic dose), and subsequent measurement of the [14C]-DNA adducts via accelerator mass spectrometry (AMS), an ultrasensitive method used for detecting rare isotopes. We postulate that adduct levels induced in tumors by GC microdoses are proportional to those formed during full dose chemotherapy. Furthermore, we hypothesize that there exists a threshold level of adducts above which tumors respond to GC therapy. We used bladder cancer cell lines and the nod scid gamma severe combined immunodeficient (NSG) mice containing patient-derived tumor xenografts (PDX) from bladder cancer patients to determine GC-DNA adduct levels using AMS. The NSG mouse is uniquely capable of accepting and propagating tumor tissue engrafted directly from patient biopsy samples. The resulting groups of mice each have identical tumors, but can be treated in a variety of ways with replicate experiments; characteristics that are impossible to achieve in normal clinical studies. We will report progress on developing protocols and preliminary GC microdosing data using the NSG-PDX mouse model of human bladder cancer. Citation Format: Maike Zimmermann, Tiffany M. Scharadin, Hongyong Zhang, Tzu-yin Lin, Ralph W. deVere White, Chong-xian Pan, Paul T. Henderson. Dual-label microdosing approach to identify chemoresistance to carboplatin and gemcitabine combination chemotherapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2821. doi:10.1158/1538-7445.AM2014-2821

Carboplatin and weekly paclitaxel chemotherapy in hemodialysis patient with advanced lung cancer and severe comorbidity: effect of the drugs and their chemical intermediates

In advanced non-small-cell lung cancer (NSCLC) patients with severe comorbidity or who are elderly, significant differences exist at the induction of chemotherapy. A 68-year-old man with a history of severe aortic stenosis and cerebral infarction had been receiving hemodialysis for end-stage renal disease. On admission due to loss of consciousness caused by aortic stenosis, a mass in the upper lobe of the right lung with a small amount of pleural effusion was detected. The patient was diagnosed with adenocarcinoma of lung (cT2bN1M1a, stage IV). A weekly regimen of paclitaxel in combination with carboplatin is less toxic than the standard regimen of administering both simultaneously. Therefore, this regimen is preferable for patients with severe comorbidity or who are elderly. For the present case, combination chemotherapy of carboplatin and weekly paclitaxel was selected and administered for four cycles. Tumor response was evaluated as stable disease and adverse events were tolerable. This combination was found to be a candidate regimen for advanced NSCLC patients receiving hemodialysis with severe comorbidity.

Effective prevention of postoperative recurrence of a granulocyte colony-stimulating factor-producing fallopian tube carcinoma by using concurrent chemoradiotherapy

Granulocyte colony-stimulating factor (G-CSF)-producing tumors are very rare in the field of gynecology and generally tend to have poor prognoses. We report a case of platinum-refractory G-CSF-producing fallopian tube cancer that was successfully treated with concurrent chemotherapy and TomoTherapy®. A 76-year-old woman with an abnormally high white blood cell (WBC) count was referred to our hospital by a local clinic. Comprehensive laboratory testing excluded a possible hematological disorder; however, on the basis of imaging findings, surgery was scheduled for a suspected fallopian tube cancer. The results of blood tests performed after the patient arrived at our hospital revealed a WBC count of 67000 cells/µL and a maximum neutrophil percentage of 96.6 %. Total hysterectomy and bilateral salpingo-oophorectomy were performed, and the histopathological analysis revealed a poorly differentiated serous adenocarcinoma of the fallopian tube. However, the postoperative blood tests revealed a G-CSF level of 183 pg/mL (normal range is <39 pg/mL). Because the preoperative WBC count and neutrophil percentage were high and the pathological specimens stained positive for G-CSF on immunohistochemical analysis, a diagnosis of a G-CSF-producing tumor was made. The tumor enlarged even though combination chemotherapy of paclitaxel and carboplatin was administered and concurrent chemoradiotherapy (CCRT) with TomoTherapy® and nedaplatin was administered. The G-CSF level increased to 852 pg/mL, after which the tumor subsequently reduced in size and the G-CSF level normalized; currently, a complete response has been maintained for 1.5 years post-surgery. This case suggests that primary TomoTherapy®-based CCRT might be effective for the treatment of G-CSF-producing tumors.

First-line and maintenance therapy for ovarian cancer: current status and future directions.

Paclitaxel and carboplatin combination chemotherapy has remained the standard of care in the frontline therapy of advanced epithelial ovarian carcinoma during the last decade. Maintenance chemotherapy or immunotherapy has not been proven to impact on overall survival and only one clinical trial that explored the administration of monthly paclitaxel for 1year showed a benefit in terms of progression-free survival (PFS), but at the cost of maintained alopecia and increased peripheral neuropathy. This scenario may be changing with the incorporation of targeted therapy to the frontline therapy of ovarian cancer. In particular, anti-angiogenic therapy has been identified as the most promising targeted therapy, and the addition of bevacizumab to first-line chemotherapy followed by a maintenance period of bevacizumab in monotherapy has shown to prolong PFS. This was considered the proof of concept of the value of anti-angiogenic therapy in the frontline of ovarian cancer, and the results of two additional clinical trials with anti-angiogenic tyrosine-kinase inhibitors have shown results in the same direction.

A case of ovarian yolk sac tumor associated with endometrioid adenocarcinoma

Ovarian yolk sac tumor (YST) is characterized by endodermal differentiation, and represents approximately 20% of malignant germ cell neoplasms. The age distribution of patients reported with YST ranges from 16 months to 46 years, but most patients are under 30 years of age (Talerman and Vang, 2011). YST is often found admixed with other types of germ cell neoplasm, but YST associated with epithelial ovarian carcinoma is extremely rare (Talerman and Vang, 2011). Unlike pure YST, YST associated with epithelial ovarian carcinoma is reported in elderly patients, and has a poor response to chemotherapy. Here we describe a case of YST associated with endometrioid adenocarcinoma in a postmenopausal woman. Our patient responded favorably to treatment with Docetaxel and Carboplatin combination chemotherapy, and has survived without evidence of relapse for 48 months postoperatively including a long term follow-up program. To the best of our knowledge, this is the first report of YST associated with endometrioid adenocarcinoma with longterm (> 48 months) successful therapy treatment, according to a Medline search of English publications.

A Case of Pulmonary Mucoepidermoid Carcinoma Responding to Carboplatin and Paclitaxel

A 59-year-old man was admitted to our hospital with dyspnea and cough. A large polypoid tumor was observed in the lower trachea and bronchoscopic polypectomy was performed using a snare to relieve symptoms. The tumor was diagnosed as a high grade mucoepidermoid carcinoma mainly by the histology of piecemeal specimens obtained by bronchoscopic resection. The primary lesion involved the trachea and the main bronchus, and there were multiple metastases in the lung. The patient was treated with the combination of carboplatin and paclitaxel. After four cycles of chemotherapy, the tumors were significantly reduced. He remains well without evidence of tumor progression for 25 months. This case suggests that the combination chemotherapy of carboplatin and paclitaxel can be an option for treatment of pulmonary mucoepidermoid carcinoma.

A Phase II Study of Paclitaxel and Carboplatin with a Biweekly Schedule in Patients with Epithelial Ovarian Cancer: Gynecologic Cancer Network Trial

The objective of this multicenter phase II study was to evaluate the effects of biweekly paclitaxel and carboplatin combination chemotherapy on response rate and toxicities in patients with epithelial ovarian cancer. Patients with International Federation of Gynecology and Obstetrics stage II to IV ovarian cancer received paclitaxel at a dose of 120 mg/m(2) and carboplatin at an area under the curve of 3 mg/mL per minute every 2 weeks for 8 or more cycles. Inclusion criteria included an Eastern Cooperative Oncology Group performance status of 0 to 2 and no previous chemotherapy. Informed consent was obtained from each patient before the start of treatment. From March 2003 through July 2009, 42 patients from 5 institutions were eligible to be evaluated for response and toxicity. The median age was 60.5 years (age range, 34-81 years). The International Federation of Gynecology and Obstetrics stage was stage II in 3 patients, stage III in 31 patients, and stage IV in 8 patients. The response rate was 66.7% (95% confidence interval: 50.5%-80.4%). Sixty-nine percent (29 of 42) of patients received 8 or more cycles of chemotherapy. The median progression-free survival was 18.5 months, and overall survival was 59.1 months. The most common grade 3 or 4 hematological toxicity was neutropenia (61.0%). No patients had grade 3 or 4 thrombocytopenia. The most common grade 3 nonhematological toxicities were neuropathy (4.9%) and nausea (2.4%). Paclitaxel combined with carboplatin using a biweekly schedule is a safe and effective chemotherapy regimen for patients with epithelial ovarian cancer. Our results suggest that a biweekly schedule is well tolerated and is less toxic than a triweekly schedule.

A case of recurrent malignant fibrous histiocytoma with marked response to combined chemotherapy with gemcitabine and carboplatin.

A case of recurrent malignant fibrous histiocytoma with marked response to combined chemotherapy with gemcitabine and carboplatin.

Chemotherapy (Gemcitabine plus Carboplatin versus Paclitaxel plus Carboplatin) in Elderly Patients with Non-Small Cell Lung Cancer

Background: This retrospective study was to evaluate the efficacy and toxicity of gemcitabine plus carboplatin (GC regimen) and paclitaxel plus carboplatin (PC regimen) combination chemotherapy in elderly patients with non-small cell lung cancer. Methods: Seventy-four patients (GC regimen, n = 44; PC regimen, n= 30) received gemcitabine at a dose of 1000 mg/m2 on days 1 and 8, and carboplatin with the target dose of area under the curve (AUC) of 4 on day 8 every 28 days and paclitaxel at a dose of 70 mg/m2 on days 1, 8 and 15, and carboplatin with the target dose of AUC of 5 on day 1 every 28 days. Patients were divided in two groups (younger one: n = 42, old; elderly one: n= 32, ≥70 years old). Results: A total of 222 cycles of the treatment wasadministered. Seventy-one patients (95.9%) completed the scheduled cycles. Two patients in the elderly group were discontinued (6.3%) due to hematological toxicity and melena in the GC regimen and to grade 4 pneumonia in the PC regimen. The dose was reduced in 8 patients (10.8%) due to grade 4 thrombocytopenia. Grade 3/4 neutropenia was not significantly observed in both groups (younger group: 24/42, 57.1%; elderly group: 19/32, 59.4%, p = 0.8471). The nonhematological toxicities were mild in both groups. However, in theelderly group, grade 3/4 thrombocytopenia was significantly observed in the GC group (GC: 5/17, 29.4%; PC: 0/15, 0.0%, p = 0.0222). There was no treatment-related death. Conclusion: These results demonstrate that the GC and PC combination chemotherapies are efficacious and feasible regimens for lung cancer therapy, especially, both regimens should be considered as one of the standard therapies for elderly patients during lung cancer therapy.

Comparison of Therapeutic G-CSF Cycles and Prophylactic G-CSF Cycles in Patients Receiving Paclitaxel and Carboplatin Combination Chemotherapy for Ovarian Cancer: A Retrospective Study Report.

Objective: The aim of the present study was to investigate the differences between therapeutic granulocyte-colony stimulating factor (G-CSF) cycles and prophylactic G-CSF cycles in patients receiving paclitaxel and carboplatin combination chemotherapy for ovarian cancer.Material and Method: Medical records of 15 women who received paclitaxel and carboplatin combination chemotherapy for ovarian cancer between January 2003 and December 2012 were analyzed retrospectively. All 15 patients completed 6 cycles of paclitaxel and carboplatin as the first-line chemotherapy. The complications were compared between therapeutic G-CSF cycles and prophylactic G-CSF cycles.Results: The number of chemotherapy cycles correlated with the ratio of prophylactic G-CSF cycles. It was considered that earlier prophylactic G-CSF injections were chosen due to a gradual decrease in WBC and neutrophil counts. The WBC and neutrophil counts were significantly higher in prophylactic G-CSF cycles than in therapeutic G-CSF cycles. However, there were no significant differences in the intervals of chemotherapy, delay of chemotherapy, and incidence of febrile neutropenia between the therapeutic G-CSF and prophylactic G-CSF cycles.Conclusion: Prophylactic G-CSF injections were not effective in preventing the incidence of febrile neutropenia in patients receiving paclitaxel and carboplatin combination chemotherapy for ovarian cancer.

Efficacy and feasibility of gemcitabine and carboplatin as first-line chemotherapy in elderly patients with advanced non-small cell lung cancer

Background Although platinum-based chemotherapy is a standard first-line treatment in advanced non-small cell lung cancer (NSCLC), further research for the safety and efficacy of combination chemotherapy in elderly patients has been required. The purpose of this study was to evaluate the efficacy and safety of gemcitabine and carboplatin as first-line treatment in elderly patients with advanced NSCLC and to evaluate the prognostic factors. Methods Eligibility included: (1) age of 70 years or more, (2) histologically confirmed NSCLC, (3) chemotherapy-naïve, (4) advanced disease with stage IIIB or IV, (5) Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, (6) adequate organ function. Patients received intravenous carboplatin (area under curve (AUC)=5) on day 1 and gemcitabine (1000 mg/m2) on days 1 and 8, every 3 weeks. Results The medical records of forty patients were reviewed retrospectively. Median age was 73.9 years (range, 70-84.6), and there were 27 men (67.5%). Thirty-seven patients (92.5%) had ECOG PS 0-1. Adenocarcinoma was found in 57.5%. Median cycles were administrated with 4.5 per person (range: 1-6). Best responses were partial response in 22 (55.0%) patients and stable disease (SD) in 13 (32.5%). The median progression free survival (PFS) and overall survival (OS) were 5.9 months (95% CI: 4.5-7.3 months) and 9.6 months (95% CI: 8.2-11.0 months), respectively. Grade 4 hematologic toxicities for neutropenia (7.5%), thrombocytopenia (7.5%) and anemia (5.0%) were observed. Histology was significant prognostic factor for PFS (P=0.024). Conclusion Gemcitabine and carboplatin combination chemotherapy is an effective and manageable treatment option in elderly advanced NSCLC patients with good performance status.

O2–105 - The Combination Chemotherapy of Carboplatin and Weekly Paclitaxel Plus Bevacizumab in Patients with Advanced NSCLC

O2–105 - The Combination Chemotherapy of Carboplatin and Weekly Paclitaxel Plus Bevacizumab in Patients with Advanced NSCLC

Abstract A55: Influence of ABCB1 polymorphisms on paclitaxel pharmacokinetics in ovarian cancer patients

Abstract Introduction: Epithelial ovarian cancer is generally treated by cytoreductive surgery followed by paclitaxel and carboplatin combination chemotherapy. Despite the high initial response rate, most patients with advanced disease will relapse and eventually succumb to illness due to intrinsic or acquired chemotherapy resistance. ABCB1 (ATP–binding cassette, sub-family B, member 1) mediates cellular elimination of many chemotherapeutic drugs, including paclitaxel. We previously reported a significant association between ABCB1 SNPs (single nucleotide polymorphisms) and PFS (progression-free survival) in ovarian cancer patients (Johnatty et al Clin Cancer Res 2008; 14: 5594-601). In patients with ≥1 cm residual disease, PFS was significantly shorter in homozygote GG carriers compared with patients who carried the minor T/A alleles at the G2677T/A locus (median PFS, 18 months compared with 32 months; p = 0.002). We hypothesized that variability in paclitaxel clearance (CL) resulting from genotypic differences in ABCB1 may underlie the impact of ABCB1 SNPs on clinical outcome. Methods: Pharmacokinetic sampling was performed during the first cycle of paclitaxel (175 mg/m2) and carboplatin (AUC5 or 6) combination chemotherapy treatment in two independent patient cohorts. These included 39 patients in a hospital based series in the Netherlands and 55 patients recruited prospectively in Australia. Paclitaxel levels were measured using liquid chromatography - tandem mass spectrometry (LC-MS/MS). The individual posterior Bayesian estimates of paclitaxel CL and model-based estimate of AUC (area-under-curve) were determined by using population pharmacokinetics with the NONMEM software. Common ABCB1 SNPs in exon 12 (C1236T), 21 (G2677T/A) and 26 (C3435T) were examined by iPLEX genotyping on Sequenom's MassARRAY platform. Nonparametric Jonckheere-Terpstra tests were used to compare the distribution of paclitaxel CL and AUC between patients of different genotypes. Results: In the Netherlands cohort, there were statistically significant associations observed between ABCB1 SNPs at exon 12 (C1236T), 21 (G2677T/A) and 26 (C3435T) and paclitaxel CL and AUC. Homozygote GG carriers at the G2677T/A locus had higher paclitaxel CL and lower AUC compared with minor T/A allele carriers. Similar findings were found for C1236T and C3435T. These findings were consistent with our previous clinical observations that patients with homozygote GG at exon 21 (G2677T/A), or homozygote CC at exon 12 (C1236T) or 26 (C3435T), had shorter PFS. The paclitaxel pharmacokinetic modeling results in the Australian cohort will be available for analysis shortly. Conclusion: The results to date suggest that common ABCB1 SNPs may contribute to chemotherapy resistance in women with ovarian cancer through their effects on paclitaxel drug disposition. Citation Format: Bo Gao, Annemieke J.M. Nieuweboer, Hongmei Xu, Jonathan Beesley, Inge M. Ghobadi Moghaddam-Helmantel, Anne-Joy M. de Graan, Peter de Bruijn, Howard Gurney, Sharon E. Johnatty, Philip Beale, Georgia Chenevix-Trench, Rosemary L. Balleine, Ron H.J. Ron H.J. Mathijssen, Paul R. Harnett. Influence of ABCB1 polymorphisms on paclitaxel pharmacokinetics in ovarian cancer patients. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A55.

Correlation of in vitro chemotherapy drug resistance assay to clinical response to carboplatin and paclitaxel combination chemotherapy in ovarian carcinoma.

e16546 Background: Carboplatin sensitivity in drug resistance assays has been shown to be an independent predictor of longer progression free interval with conflicting results in overall survival. We evaluated in vitro drug resistance for carboplatin and paclitaxel combination and its correlation with progression free survival (PFS) and overall survival (OS). Methods: From April 1, 2006 to December 12, 2011, in vitro drug resistance assays were sent after cytoreductive surgery for primary epithelial ovarian cancer. Patients were analyzed according to drug resistance scoring system of low drug resistance (S), intermediate drug resistance (I), and extreme drug resistance (R). Retrospective chart review was performed to evaluate PFS and OS. The Kaplan Meier product limit method was used to estimate OS and PFS. Survival curves were compared between groups using the log rank test. Results: From a total of 142 patients: 57 were S, 52 I, and 33 R; 77% were responsive (S+I) to carboplatin and paclitaxel combination. At median follow-up of 18 months, PFS and OS rates were 58.1 and 91.3% respectively for S, 66.1 and 78.7% for I, and 43.2% and 84.3% for R. At 36 months, the PFS and OS rates were 52.3 and 61.1% for S, 51.3 and 55.3% for I and 39.3% and 48.7% for R. There was OS advantage between the S and I compared to R. There were no significant differences in PFS curves (p&lt;0.281) or OS curves (p&lt;0.46). Conclusions: Although sensitivity to carboplatin/ paclitaxel resulted in longer OS, the results were not statistically significant. Our cohorts were small and we may not have had the power to capture statistical significance. A larger multicenter analysis would be needed to further evaluate this finding. In addition, one of the regimens our patients received on relapse was bevacizumab which was not evaluated in the in vitro assay sensitivity assay. Bevacizumab has also been included in first line treatment in combination with platinum/ taxane regimen. Future analysis of in vitro assays may need to include biologics.

Abstract 949: miR-634 restores drug sensitivity in tumor cells derived from patients with terminal drug-resistant ovarian cancer.

Abstract The development of drug resistance is still a major impediment for the successful treatment of cancer. This is particularly pressing in the case of advanced ovarian cancer, which has a 5-year survival rate of 30%. Ovarian cancer is treated with paclitaxel and platinum (e.g cisplatin or carboplatin) combination chemotherapy. Despite an initial high chemo-responsiveness, most ovarian cancer patients will relapse and ultimately die of drug-resistant disease. The molecular processes that contribute to resistance have been extensively studied, however, not much is known about the role of microRNAs (miRNAs), small non-coding RNAs that regulate gene expression. We compared miRNA expression profiles of isogenic cisplatin sensitive and resistant cell line pairs. The only miRNA that was consistently downregulated in all three resistant cell lines was miR-634 (FDR&amp;lt;1%). Overexpression of miR-634 in ovarian cancer cell lines gave rise to a minor, but reproducible, cell cycle block and reduced cellular viability by 20-50%. In addition, miR-634 transfection resensitized cisplatin-resistant ovarian cancer cell lines. We next investigated whether miR-634 overexpression could enhance therapy response in a more clinical setting. We isolated and cultured tumor cells from 7 patients that had become refractory to carboplatin-paclitaxel combination chemotherapy. We show that miR-634 overexpression causes a ∼two-fold decrease in IC50 for cisplatin and carboplatin treatment. In addition, a ∼1.3-fold decrease in doxorubicin sensitivity was observed upon miR-634 overexpression. Finally, overexpression of miR-634 resulted in downregulation of its predicted targets Cyclin D1 and GRB2, ERK2, RSK1 and RSK2, components of the Ras-MAPK pathway. The combined effect on these miR-634 targets may explain the effects on the cell cycle, cellular viability and response to chemotherapy. Altogether, our findings suggest that miR-634 modulates important cancer relevant targets and that raising miR-634 levels can be a means to resensitize chemotherapy resistant ovarian tumors. Citation Format: Marijn TM van Jaarsveld, Patricia F. van Kuijk, Antonius WM Boersma, Jozien Helleman, Wilfred F. van Ijcken, Ron HJ Mathijssen, Joris Pothof, Els MJJ Berns, Jaap Verweij, Erik AC Wiemer. miR-634 restores drug sensitivity in tumor cells derived from patients with terminal drug-resistant ovarian cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 949. doi:10.1158/1538-7445.AM2013-949

Comparative analysis of carboplatin and paclitaxel combination chemotherapy schedules in previously untreated patients with advanced non-small cell lung cancer

The combination of carboplatin and paclitaxel is one of the most commonly used regimens for the treatment of non-small cell lung cancer (NSCLC). We aimed to compare the standard tri-weekly and weekly schedules of this treatment, while considering treatment-related hematological toxicities. We retrospectively analyzed the weekly [paclitaxel, 70 mg/m2/week on days 1, 8 and 15, and carboplatin, area under the curve (AUC)=6, every 4 weeks] and standard tri-weekly (paclitaxel, 200 mg/m2, and carboplatin, AUC=6, on day 1 every 3 weeks] schedules in patients with previously untreated advanced NSCLC. A total of 167 patients were enrolled in this study. The median age of the patients was 65 years (range, 31–79 years). The weekly and standard arms included 73 and 94 patients, respectively. The incidence of grade 3 or 4 neutropenia and neuropathy was significantly decreased in the weekly arm compared with the standard arm (37.0 vs. 70.2%). The median survival and progression-free survival times were 11.8 and 4.2 months, respectively, in the weekly arm and 11.6 and 3.1 months, respectively, in the standard arm. The results of the multivariate analysis indicated that the weekly schedule [hazard ratio (HR)=0.634, P=0.0262] and grade 3 or 4 neutropenia (HR=0.372, P=0.0007) were independent favorable prognostic factors for overall survival time. In conclusion, the weekly schedule of carboplatin and paclitaxel was less toxic than and potentially superior to the standard tri-weekly schedule. However, further optimization of the dose and schedule is warranted.

A case of a hemodialysis patient with ovarian cancer treated with paclitaxel and carboplatin combination chemotherapy

A case of a hemodialysis patient with ovarian cancer treated with paclitaxel and carboplatin combination chemotherapy

A feasibility study on maintenance of docetaxel after paclitaxel-carboplatin chemotherapy in patients with advanced ovarian cancer

ObjectiveTo test the concept of taxane sequencing, this feasibility trial evaluated maintenance of docetaxel after paclitaxel and carboplatin combination chemotherapy in patients with stage IC-IV ovarian cancer.MethodsAll patients received debulking surgery followed by paclitaxel and carboplatin chemotherapy. Attainment of clinically defined complete or partial response was confirmed by image scanning. Maintenance of docetaxel started at an initial dose of 70 mg/m2 every 4 weeks for 6 cycles and was extended to 10 cycles unless disease progression and/or recurrence during the protocol therapy or unacceptable toxicities were seen.ResultsStage subsets in 20 eligible patients were as follows: IIIB, 2 patients (10%); IIIC, 13 patients (65%); IV, 5 patients (25%). Neutropenia was common (40% with grade 3 or 4) and was most frequent during first or second cycle although the disabling peripheral neuropathy was not observed. Twelve patients completed protocol therapy (6≤cycles), while 8 patients failed to complete 6-cycle chemotherapy, because of progressive disease (5 patients) or grade 4 toxicities (3 patients). Median PFS was 20 months and 3-year PFS rate was 12%. Median overall survival was 39 months and 3-year OS rate was 69%.ConclusionSix cycles of single-agent docetaxel maintenance chemotherapy is feasible and generally tolerable to women with advanced ovarian cancer who attained a clinically defined response to initial paclitaxel and carboplatin based chemotherapy.

Adjuvant Chemotherapy of Gemcitabine plus Carboplatin versus Paclitaxel plus Carboplatin in Patients with Resected Non-Small Cell Lung Cancer

Background: This retrospective study was to evaluate the efficacy and toxicity of gemcitabine plus carboplatin (GC regimen) and paclitaxel plus carboplatin (PC regimen) combination chemotherapy administered as an adjuvant therapy after complete resection of non-small cell lung cancer. Methods: Forty-four patients (GC regimen, n = 29; PC regimen, n = 15) received gemcitabine at a dose of 1000 mg/m2 on days 1 and 8, and carboplatin with the target dose of area under the curve (AUC) of 4 on day 8 every 28 days and paclitaxel at a dose of 70 mg/m2 on days 1, 8 and 15, and carboplatin with the target dose of AUC of 5 on day 1 every 28 days. Results: A total of 130 cycles of the treatment were administered (averaged, 3.1 in GC arm and 2.7 cycles in PC arm). Forty-three patients (97.7%) completed the scheduled cycles. One patient (2.3%) was discontinued due to grade 4 pneumonia. The dose was reduced in 2 patients (4.5%) due to grade 4 thrombocytopenia. Grade 3/4 neutropenia was significantly observed in the PC group (GC: 12/29, 41.4%; PC: 11/15, 73.3%, p = 0.0443). The nonhematological toxicities were mild. Grade 1/2 alanine aminotransferase and aspartate aminotransferase in the GC group was significantly observed higher compared to those of the PC group (GC: 20/29, 69.0%; PC: 4/15, 26.7%, p = 0.0076). Grade 1/2 alopecia was significantly observed in the PC group (GC: 0/25, 0.0%; PC: 13/15, 86.7%, p 0.0001). There was no treatment-related death. The median survival time (MST) of the entire GC group was 784 days, the 3-year overall survival (OS) was 75.9%, and 3-year recurrence-free survival (RFS) was 65.5%. The MST of the entire PC group was 963 days, the 3-year OS was 80.0%, and the 3-year RFS was 60.0%. Conclusion: These results demonstrate that the GC and PC combination chemotherapies are efficacious and feasible regimens, which should be considered as one of the standard therapies for adjuvant therapy.