Paclitaxel Regimen Research Articles

A Rare non-auto immunodeficiency disease (AIDS) related neo-plasm Kaposi sarcoma in Iraqi man: a case report

The aim of this article is to report unusual case of KS presenting in the patient with negative serology for AIDS. Kaposi Sarcoma (KS) is a rare entity. It is a vascular neoplasm mainly affecting the skin of the lower extremities. Although it is the most common neoplasm affecting patients with AIDS, sporadic cases in HIV-negative people have been reported but it is rare. Here, we present a case of a non-auto immunodeficiency disease (AIDS) related KS. A 72 year-old male, Iraqi patient presented to our oncology outpatient’s unit in Al-Shafaa Oncology Center with multiple subcutaneous nodules. The diagnosis was based on histopathological and immunohistochemical analysis of the excised lesion, serology tests and imaging investigations. The patient had a 13-month history of a slowly progressing pigmented multiple lesions on the lower and upper extremities. The patient had visceromegaly as splenomegaly at the time of presentation. His serum was negative for the common types of viral infections including Human Immunodeficiency Virus (HIV) on routine serology. On general examination, the man look well, no pallor, no fever, no cachexia present and no jaundice. There are a multiple ill defined, irregular hyper-pigmented nodules to plaques were present on forearm, legs, feet and hands. The nodules and plaque was firm in consistency and was non-tender. The lesions were deep reddish to brownish in color. The size of the lesions were arranged from 0.5-1.5 cm. No scaling was evident. The patient was under treatment with chemotherapeutic regimen of Paclitaxel.Â

Weekly nanoparticle albumin-bound paclitaxel(nab-PTX) as second-or later-line treatment for unresectable or recurrent gastric cancer in practice.

168 Background: Nanoparticle albumin-bound paclitaxel (nab-PTX) is a novel, solvent polyoxyethylated castor oil-free, biologically interactive form of paclitaxel (PTX). Nab-PTX allows shorter infusion schedules and needs no premedication for hypersensitivity reactions, so nab-PTX will be used as the alternative to PTX for more patients. In Japan, nab-PTX was approved as tri-weekly regimen (210mg/m2 every 3weeks) for gastric cancer. On the other hands, weekly PTX (80mg/m2 on day1, 8, and 15, every 4weeks) is mostly used as PTX regimen as 2nd or later line treatment for gastric cancer in Japan. So in practice, nab-PTX would be used by weekly regimen same as weekly PTX. However, the safety and efficacy of weekly nab-PTX for gastric cancer had not been reported yet. Methods: Unresectable or metastatic gastric cancer patients who began receiving weekly nab-PTX as 2nd or later line chemotherapy in our two facilities from February 2013 to August 2014 were retrospectively analyzed for the safety and efficacy. Written informed consent about the treatment of weekly nab-PTX was obtained from all patients before treatment. Results: A total of 32 patients were assessed, retrospectively. The dose and schedule of nab-PTX was 100mg/m2 on day1, 8, and 15, every 4weeks in all patients. Patients characteristics were as follows: median age 67.5(37-84); Male/female: 24/8; PS 0/1/2/3:15/8/7/2; treatment line 2/3/4/5: 12/14/5/1. The overall response rate was 9.3% (CR/PR/SD/PD/NE: 1/2/12/15/2). The median progression-free survival (mPFS) and median overall survival (mOS) were 2.99 months and 5.95 months, in all patients. In 23 patients whose PS were 0 or 1, mPFS and mOS were 4.14 months and 8.44 months. Most common grade 3/4 hematological toxicities were anemia (46.9%), neutropenia (40.6%), febrile neutropenia (15.6%). About the sensory neuropathy, grade 3 was 9.3%, grade2 was 21.9%, and grade1 was 3.1%. There were no treatment-related deaths. Conclusions: Weekly nab-PTX showed promising efficacy against previously treated unresectable or recurrent gastric cancer especially for good PS patients, The Common toxicities of weekly nab-PTX were well-tolerated.

Positive expression of pro-opiomelanocortin (POMC) is a novel independent poor prognostic marker in surgically resected non-small cell lung cancer.

This study aims to investigate the expression level of pro-opiomelanocortin (POMC) and its prognostic value in non-small cell lung cancer (NSCLC). Immunohistochemical staining was used to detect the expression level of POMC. Correlations between POMC expression and clinical and pathological characteristics were evaluated with the chi-square test, and the prognostic value was determined with the Kaplan-Meier method and COX proportional hazards model, α < 0.05. Of the samples, 48.0% had positive POMC expression. POMC expression was significantly related to poorly differentiated tumors, N-stage, p-stage, postoperative failure pattern, expression of vimentin, and expression of E-cadherin (P < 0.05). Multivariate analysis revealed that POMC-positive expression was an independent risk factor for disease-free survival (hazard ratio (HR) 1.988, 95% confidence interval (CI) 1.094-3.910, P = 0.024) and overall survival (HR 1.892, 95% CI 1.726-3.709, P = 0.036). The addition of POMC protein expression to the prognostic model using pathological stage markedly improved the prognostic potential, and the area under the ROC increased from 0.691 to 0.775. Further study revealed that patients with POMC-negative expression can benefit more from a regimen of paclitaxel and carboplatin chemotherapy than a regimen of vinorelbine and carboplatin compared to patients with POMC-positive expression. We found that POMC-positive expression is a novel, independent poor prognostic marker in patients with NSCLC. Prospective studies are needed to validate the potential prognostic value of POMC in combination with the current staging system and in consideration of adjuvant chemotherapy.

The efficacy and toxicity of paclitaxel plus S-1 compared with paclitaxel plus 5-FU for advanced gastric cancer: a PRISMA systematic review and meta-analysis of randomized controlled trials.

The standard treatment for patients with advanced gastric cancer (AGC) is still a matter of debate. The chemotherapy regimen of paclitaxel (PTX) combined with S-1 has been used to treat AGC or metastatic gastric cancer.We conducted a meta-analysis to compare oral S-1 and infusional 5-fluorouracil (5-FU) to determine which agent was more efficacious and less toxic in combination with PTX. A systematic review with a meta-analysis was performed. PubMed, EmBase, the Cochrane Central Register of Controlled Trials, and the China National Knowledge Infrastructure databases were searched to select randomized controlled trials (RCTs) comparing PTX plus S-1 and PTX plus 5-FU in patients with AGC.Three RCTs were eligible and 352 patients were analyzed. PTX plus S-1 increased the disease control rate (risk ratio [RR] = 1.14, 95% confidence interval [CI] = 1.00–1.30, P = 0.04) and reduced the progressive disease rate (RR = 0.62, 95% CI] = 0.39–0.98, P = 0.04) compared with PTX plus 5-FU. There was a significant decrease in nausea (RR = 0.60, 95% CI = 0.43–0.82, P = 0.001) and vomiting (RR = 0.55, 95% CI = 0.33–0.91, P = 0.02) in patients treated with PTX plus S-1.PTX plus S-1 was associated with almost equivalent safety and a lower progressive disease rate compared with PTX plus 5-FU. PTX plus S-1 is a good alternative strategy for patients who cannot tolerate a continuous intravenous infusion.

Prevalence of Febrile Neutropenia in Breast Cancer Patients Received Adjuvant Paclitaxel Treatment.

OBJECTIVE: to review prevalence and risk factors of febrile neutropenia in breast cancer patients received adjuvant paclitaxel treatment. METHODS: retrospective chart review of 18 breast cancer patients received 146 cycles of adjuvant paclitaxel for prevention of breast cancer recurrence during 2011 at Phramongkutklao hospital, Bangkok, Thailand. RESULTS: Average age of patient in this study was 54.6+/-10.5 years old. Paclitaxel were given to patients in 7 dosage regimens. The most common dosage regimen (62/146, 42.5%) was weekly paclitaxel 12 cycles post doxorubicin and cylcophosphamide (AC) regimen. There were 3 febrile neutropenia cases out of 18 patients who received 146 cycles of adjuvant paclitaxel treatment. Prevalence of febrile neutropenia in this study was 2.05%. Prevalence of neutropenia in this study was 7.5% (11 cases out of 146 treatment cycles). Dosage regimen of paclitaxel (> 100 mg/m2 /cycle ) was found to associated with neutropenia. Other common adverse events found in this study were peripheral neuropathy in 9 cases (50%), nausea/vomiting 7 cases (29%) and muscle weakness 6 cases (25%). CONCLUSIONS: Neutropenia from higher dose (>100 mg/m2) of paclitaxel was common and trend to associated with febrile neutropenia in breast cancer patients treated with this drug. Closely monitoring and supportive therapy is needed in the patients recieving higher paclitaxel dose to prevent febrile nutropenia during adjuvant paclitaxel treatment. Rationale Paclitaxel is a fundamental drug for breast cancer treatment. It prolongs patients’ survival and prevents disease recurrence, either alone or in combination with other antinoeplastics. Despite its effectiveness, adverse effects such as hypersensitivity, peripheral neuropathy and bone marrow suppression are common and should be well monitored in patients received the treatment. Among several toxicities, febrile neutropenia can be fatal and should be studied to explore the prevalence and risk factors for improving the safety in patients who need paclitaxel treatment. Objectives To review the prevalence and risk factors associated with febrile neutropenia among breast cancer patients received adjuvant paclitaxel treatment in real practice setting. Methods This study was done by retrospective chart review in randomly selected accessible 18 patients received adjuvant paclitaxel treatment during year 2011. Results Discussion and Conclusion Prevalence of febrile neutropenia and neutropenia was 2.05% and 7.5%, respectively in this study. The prevalence of febrile neutropenia was relatively low when compare to similar studies. However, focusing on neutropenia, the prevalence of neutropenia in patients received AC/T regimen was comparative to similar study. We found lower prevalence of neutropenia (8.06% vs 10.34%) among patients received weekly paclitaxel compare to who received every 3 weeks paclitaxel which indicated impact of the dose on neutropenia adverse effect. When focusing to the dose of paclitaxel, the higher dose (>100 mg/m2 /cycle) was found to associated with higher prevalence of neutropenia. Therefore, close monitoring and supportive treatment are warranted for patient receiving paclitaxel especially in the high dose/cycle (> 100mg/m2).

P2-3-5 - Bevacizumab Plus Paclitaxel for Her2 Negative Advanced/Recurrent Breast Cancer: Assessment of Efficacy and Safety

Background: Bevacizumab(BV) combined with paclitaxel(PAC) is one of a useful option to manage HER2 negative advanced/recurrent breast cancer(HER2-BC). However, importance of toxicity management have not been well discussed.Patients and methods: Patients(pts) having HER2-BC were considered to receive BV + PAC regimen. To avoid neurotoxicity, PAC was administered biweekly at the dose of 100mg/body. Additional PAC on day 8 for initial 2 or 3 cycles was applied to pts with emerging disease. BV was administered biweekly at the dose of 10mg/kg concurrently with PAC.Results: From October 2011 to December 2013, median age of 52(range 29-74), 50 female pts received BV + PAC. Estrogen receptor(ER) was positive in 38pts(76.0%), and 12pts(24.0%) revealed triple-negative. Median Ki67 rate was 25.4%(range 2.0-98.5). Disease statuses were as follows; recurrent 31 (62.0%), advanced 19(38.0%), visceral lesion(s) 30(60.0%), prior taxane 29(58.0%). Objective response rate(ORR) was 40.0%. Median time to treatment failure(TTF) was 195.0 days(95% confidence interval[CI] 89.0-364.0). In 20pts who received BV + PAC as 1st-line, ORR was 70.0% and median TTF was 321.0 days (95%CI 154.0-503.0). TTF was independent from ER, Ki67, visceral lesion or prior taxane. Gr2/3 HT associated with BV was seen in 23pts(46.0%), and they showed strong trend of superior TTF compared to pts with Gr0/1 HT regardless of treatment-line(P = 0.065, log-lank). Gr3 proteinuria was seen in 3pts and it was maintained by reduction of BV. Other toxicities were tolerable and no Gr3 sensory neuropathy or Gr4 HT was seen. However, 1pt with Gr2 neuropathy withdrew from the therapy due to the toxicity.Conclusions: We conclude 1) BV combined with dose-reduced PAC have a potential to control HER2-BC with less toxicity compared to conventional BV + PAC, and 2) treatement-related Gr2/3 HT is one of the significant predictive marker of BV + PAC therapy in HER2-BC.

O3-9-1 - Weekly Paclitaxel in Combination with Bevacizumab in Patients with Non-Sq Nsclc Who Have Failed Previous Treatments

Backgrounds: Bevacizumab (BEV) in combination with paclitaxel (PTX) and carboplatin (Cb) has provided survival benefit for advanced non-small cell lung cancer (NSCLC) as first-line treatment. However, tri-weekly PTX therapy induce severe peripheral neuropathy frequently, and may deteriorate quality of life. Because of this toxicity, platinum plus pemetrexed regimen may be preferred as first-line treatment over Cb/PTX/BEV regimen. Weekly paclitaxel (w-PTX) regimen has proved to be effective and safe in a large number of clinical trials for advanced solid tumors. However, few clinical studies have focused on the comparison between w-PTX and tri-weekly PTX in advanced NSCLC. We previously reported that fractionated administration of paclitaxel may be less toxic and more active against advanced NSCLC in clinical trials. Furthermore, several studies have reported that combination chemotherapy of w-PTX and BEV proved survival benefit in patients with advanced breast cancer. Therefore, we conducted a phase II trial to evaluate the efficacy and toxicity for the combination chemotherapy of w-PTX and BEV in patients with advanced non-squamous (non-Sq) NSCLC who have failed previous treatment.Methods: Eligibility required ECOG performance status 0-2 and prior cytotoxic chemotherapy. The primary end point of the phase II study was the progression free survival (PFS). PTX was infused on days 1, 8 and 15, and BEV (15 mg/kg) was administered on day 1 of a 4-week cycle until PD. Toxicity evaluations were based on CTCAE (version 4).Results: Between September 2011 and January 2014 a total of 30 eligible patients were enrolled onto the study.Conclusions: This combination of w-PTX and BEV is both feasible and active in the treatment of patients with advanced non-Sq NSCLC. We will soon start a phase II study evaluating this combination as first-line treatment.

Thiamet-G-mediated inhibition of O-GlcNAcase sensitizes human leukemia cells to microtubule-stabilizing agent paclitaxel

Although the microtubule-stabilizing agent paclitaxel has been widely used for treatment of several cancer types, particularly for the malignancies of epithelia origin, it only shows limited efficacy on hematological malignancies. Emerging roles of O-GlcNAcylation modification of proteins in various cancer types have implicated the key enzymes catalyzing this reversible modification as targets for cancer therapy. Here, we show that the highly selective O-GlcNAcase (OGA) inhibitor thiamet-G significantly sensitized human leukemia cell lines to paclitaxel, with an approximate 10-fold leftward shift of IC50. Knockdown of OGA by siRNAs or inhibition of OGA by thiamet-G did not influence the cell viability. Furthermore, we demonstrated that thiamet-G binds to OGA in competition with 4-methylumbelliferyl N-acetyl-β-d-glucosaminide dehydrate, an analogue of O-GlcNAc UDP, thereby suppressing the activity of OGA. Importantly, inhibition of OGA by thiamet-G decreased the phosphorylation of microtubule-associated protein Tau and caused alterations of microtubule network in cells. It is noteworthy that paclitaxel combined with thiamet-G resulted in more profound perturbations on microtubule stability than did either one alone, which may implicate the underlying mechanism of thiamet-G-mediated sensitization of leukemia cells to paclitaxel. These findings thus suggest that a regimen of paclitaxel combined with OGA inhibitor might be more effective for the treatment of human leukemia.

Clinical Significance of Cytological Status of Peritoneal Lavage Fluid During Intraperitoneal Chemotherapy for Gastric Cancer with Overt Peritoneal Dissemination

A positive cytology of peritoneal lavage fluid (CY1) is a poor prognostic factor in patients with gastric cancer (GC). We have recently reported that CY1 often changes to negative (CY0) following combination chemotherapy including intraperitoneal (IP) paclitaxel (PTX), which results in marked prolongation of survival in GC patients with peritoneal dissemination (P1). A total of 95 P1 GC patients who received combination chemotherapy with S-1 and intravenous and IP PTX were enrolled. Peritoneal lavage fluid was periodically examined cytologically at the start of every cycle of chemotherapy, and the impact of CY status on patient outcome was retrospectively evaluated. Seventy-three (76.8%) of 95 patients were diagnosed as CY1 before initial treatment. Median survival time (MST) of the CY1 group was significantly shorter than that of the CY0 group (19.1 vs. 32.5 months, P = 0.033). Cytological status changed from CY1 to CY0 in 68 (93.2%) of 73 CY1 patients during the whole treatment period and MST of patients who showed a negative change was significantly longer than that of the unchanged group (20.0 vs. 13.0 months, P = 0.0017). In 64 patients who achieved CY0 by IP PTX regimen, the median time to achieve CY0 was 1.4 months, and patients who achieved a negative change within 1 month showed a particularly good outcome (MST = 26.1 months). Periodic cytological examination of peritoneal lavage fluid is clinically useful to evaluate the efficacy of treatment as well as to predict the outcome of patients with P1 GC.

Second Line Treatment in Small-Cell Lung Cancer (Sclc) Patients: Single Center 10-Years Experience and Feasibility of Epirubicin Plus Paclitaxel Regimen

Second Line Treatment in Small-Cell Lung Cancer (Sclc) Patients: Single Center 10-Years Experience and Feasibility of Epirubicin Plus Paclitaxel Regimen

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.

Predictive value of APE1, BRCA1, ERCC1 and TUBB3 expression in patients with advanced non-small cell lung cancer (NSCLC) receiving first-line platinum-paclitaxel chemotherapy.

Drug resistance is not only one of the major obstacles to treatment but also a poor prognosis in advanced non-small cell lung cancer (NSCLC) patients. The aim of this study was to evaluate the predictive value of APE1, BRCA1, ERCC1 and TUBB3 in advanced NSCLC patients who received platinum-paclitaxel treatment. One hundred and thirty-six advanced NSCLC patients, who were treated with first-line platinum-paclitaxel chemotherapy, were enrolled in this study. The protein expression levels of APE1, BRCA1, ERCC1 and TUBB3 were assessed by immunohistochemistry and analyzed for the association with response to chemotherapy and progression-free survival (PFS) and overall survival (OS). Patients with negative expression of APE1, ERCC1 or TUBB3 benefited from platinum plus paclitaxel regimen chemotherapy. ERCC1-negative patients had better PFS (P = 0.016) and OS (P = 0.030) compared with positive patients. Similarly, the APE1-negative patients showed better PFS (P = 0.004) and longer OS though statistically insignificant. Multivariate analysis showed that APE1 and ERCC1 were independent predictor for PFS (HR 2.07; P = 0.004 and HR 1.66; P = 0.016) and OS (HR 1.99; P = 0.008 and HR 1.64; P = 0.040). Moreover, patients with both APE1- and ERCC1-negative or both APE1- and TUBB3-negative tumors had significantly higher response rate, longer median PFS and OS following treatment with platinum and paclitaxel (P < 0.05). The data indicate that APE1, ERCC1 and TUBB3 could be a useful biomarker to predict clinical outcome in patients with advanced NSCLC receiving first-line platinum-paclitaxel chemotherapy.

PRELIMINARY RESULTS OF A PROSPECTIVE FEASIBILITY PILOT STUDY OF "GEMPOX" (GEMCITABINE, OXALIPLATIN, AND PACLITAXEL) IN PEDIATRIC AND ADULT PATIENTS WITH REFRACTORY OR RECURRENT CENTRAL NERVOUS SYSTEM (CNS) GERM CELL TUMORS (GCT): THE INTERNATIONAL CNS GCT CONSORTIUM TRIAL, CNS GCT-4

BACKGROUND: The optimal management of patients with recurrent CNS GCT, especially those with non-germinomatous (mixed malignant) GCT (MMGCT), remains unclear. Preliminary results are presented on the response rate, toxicity and early outcomes of a re-induction regimen of gemcitabine, oxaliplatin and paclitaxel (GEMPOX) administered, in responsive patients, prior to myeloablative chemotherapy and autologous hematopoietic cell rescue (HDCx + AuHCR). METHODS: Since December 2004, 13 recurrent or refractory patients (12 MMGCT, 1 germinoma; 12 males; mean age 16.5 years, range 7-34 years) have been treated with up to 4 cycles of gemcitabine (800 mg/m2), oxaliplatin (100 mg/m2) and paclitaxel (170 mg/m2), administered on one day at 14 days intervals. RESULTS: Of 13 patients, five were treated on a preceding feasibility pilot with 1-3 cycles of GEMPOX, and seven have been formally enrolled on an ongoing prospective multi-center trial. Six patients achieved complete remissions (tumor marker and/or imaging studies), five achieved partial remissions and two developed progressive disease (PD) while on GEMPOX; one patient with PD after 1 cycle had pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma.; the second patient, with pure pineal choriocarcinoma, progressed following the second cycle of GEMPOX. Eleven of the 13 patents subsequently underwent HDCx + AuHCR. Six of them subsequently received irradiation. Transient hepatotoxicity and pancytopenia were the most commonly observed toxicities. Other toxicities included: paclitaxel anaphylaxis (1), transient encephalopathy (1), peripheral neuropathy (1), hyperesthesia (4), mucositis (2) and electrolyte imbalances (3). Four of the 12 patients with MMGCT continue alive and disease-free for 8+ , 10+ , 14+ and 16+ months since discontinuation of all therapy. One patient (with pure yolk sac tumor) relapsed in a loco-regional extra-CNS location (cavernous and ethmoid/sphenoid sinuses) and remains alive with progressive disease on therapy now 12+ months post-HDCx + AuHCR. CONCLUSIONS: GEMPOX appears to be an effective re-induction regimen for patients with recurrent CNS MMGCT, with acceptable toxicities. The ongoing multi-center, international trial should confirm this and demonstrate the contribution of GEMPOX towards improved survival when followed by HDCx + AuHCR with or without further irradiation, in the setting of minimal residual disease. SECONDARY CATEGORY: Pediatrics.

Cetuximab in advanced non-small cell lung cancer (NSCLC): the showdown?

Cetuximab in advanced non-small cell lung cancer (NSCLC): the showdown?

A dose-dense paclitaxel and carboplatin regimen is highly active in the treatment of recurrent and advanced endometrial cancer

A dose-dense paclitaxel and carboplatin regimen is highly active in the treatment of recurrent and advanced endometrial cancer

Paclitaxel combined with capecitabine as first-line chemotherapy for advanced or recurrent gastric cancer.

Chemotherapy is of crucial importance in advanced gastric cancer (AGC) patients, in order to obtain palliation of symptoms and improve survival. To date, no standard chemotherapy regimen has been established for AGC. The purpose of the present study was to evaluate the efficacy and toxicity of the combination regimen of paclitaxel and capecitabine (PX) as first-line chemotherapy in patients with advanced or recurrent gastric cancer. Patients with advanced or recurrent gastric cancer who were treated with PX as first-line chemotherapy between January 2001 and December 2012 at the Zhejiang Cancer Hospital (Hangzhou, China) were retrospectively investigated. Survival was evaluated using the Kaplan-Meier method. In total, 36 patients were enrolled, with a median age of 53.5 years and a Karnofsky performance status (KPS) score of ≥80. A median of 4 PX cycles were administered (range, 2–8 cycles). The median progression-free survival time was 3.7 months [95% confidence interval (CI), 2.9–4.5 months) and the median overall survival time was 12.0 months (95% CI, 9.8–14.1 months). From the 36 patients evaluated, one (2.8%) achieved a complete response, seven (19.4%) achieved a partial response, 24 (66.7%) exhibited stable disease and four (11.1%) exhibited progressive disease. The objective response rate was 22.2% (8/36), and the disease control rate was 88.9% (32/36). All 36 patients were assessed for treatment toxicity. Grade 3 or 4 adverse events included neutropenia (2.8% of patients), hand-foot syndrome (2.8%) and vomiting (2.8%). No neutropenic fever or treatment-related mortalities were observed. PX combination chemotherapy may be a valuable first-line therapy for advanced or recurrent gastric cancer.

Model-based meta-analysis for quantifying Paclitaxel dose response in cancer patients.

Model-based meta-analysis of dose response is a sophisticated method to guide dose and regimen selection. In this report, the effects of paclitaxel dose and regimen (weekly or every 3 weeks) on the efficacy and safety in cancer patients were quantified by model-based meta-analysis of 29 monotherapy trials. Logistic regression models were developed to assess the relationship between dose and objective response rate or neutropenia rate. Survival models were developed to assess the relationship between dose and overall survival or progression-free survival. Paclitaxel efficacy (e.g., objective response rate, median overall survival, and progression-free survival) is correlated with average dose per week (mg/m2/week), whereas safety (e.g., neutropenia rate) is correlated with dose per administration (mg/m2). Weekly paclitaxel regimen at 65–80 mg/m2 is supported to have comparable to better efficacy and lower neutropenia incidence than an every-3-week regimen at 175 mg/m2.

OP0012 Chemotherapy with gefitinib in recurrent and metastatic head and neck cancer

Background We aimed to evaluate the efficacy and toxicity profile of a paclitaxel and platinum-based chemotherapy regimen in combination with oral targeted therapy (gefitinib) in patients with recurrent and metastatic head and neck squamous cell carcinoma (HNSCC). Methods 70 patients (57 male, 13 female) with recurrent and metastatic HNSCC with ECOG performance status of 0–2 were prospectively recruited to this study. They were given chemotherapy (weekly paclitaxel at a dose of 80 mg/m 2 and cisplatin 35 mg/m 2 or carboplatin at a dose of AUC 1.5 on days 1, 8, and 15 every 4 weeks for a maximum of six cycles) in combination with the oral targeted therapy gefitinib, 250 mg daily. All patients were evaluated after three cycles and six cycles with imaging (MRI/CT/PETCT), comparing with baseline to assess response as per RECIST criteria. Additionally, toxic effects according to CTC criteria were studied. Findings On response evaluation, overall response rate (complete plus partial response) was 44.3%, with stable disease in 25.7% and progression in 30% of patients. Median progression-free survival was 4.8 months (5.9 months in patients with complete or partial response) and median overall survival was 9.5 months (11 months in patients with complete or partial response). The main toxicities were haematological and gastrointestinal, which were manageable. Interpretation The addition of the oral tyrosine kinase inhibitor gefitinib to a platinum-based doublet chemotherapy for recurrent and metastatic HNSCC is a feasible and well tolerated regimen with good response and outcome that should be tried in large cohort of patients.

Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trial

Carboplatin plus paclitaxel administered every 3 weeks is standard first-line chemotherapy for patients with advanced ovarian cancer. A weekly paclitaxel schedule combined with carboplatin every 3 weeks prolonged progression-free survival and overall survival in a Japanese phase 3 trial. The aim of our study was to assess whether a weekly schedule of carboplatin plus paclitaxel is more effective than the same drugs given every 3 weeks. We did a multicentre, randomised, phase 3 study at 67 institutions in Italy and France. Women with FIGO stage IC-IV ovarian cancer, an ECOG performance status of 2 or lower, and who had never received chemotherapy were randomly allocated in a 1:1 ratio to receive either carboplatin (AUC 6 mg/mL per min) plus paclitaxel (175 mg/m(2)) every 3 weeks for six cycles or carboplatin (AUC 2 mg/mL per min) plus paclitaxel (60 mg/m(2)) every week for 18 weeks. Randomisation was done by computer-based minimisation, stratified by centre, residual disease after surgery, and ECOG performance status. The study was not blinded. Coprimary endpoints were progression-free survival and quality of life (assessed by the Functional Assessment of Cancer Therapy Ovarian Trial Outcome Index [FACT-O/TOI] score), and analysis was by modified intention to treat. This report presents the final analysis. The study is registered with ClinicalTrials.gov, number NCT00660842. 822 patients were enrolled into the study between Nov 20, 2008, and March 1, 2012; 12 withdrew their consent immediately after randomisation and were excluded, and 810 were eligible for analysis. 404 women were allocated treatment every 3 weeks and 406 were assigned to the weekly schedule. After median follow-up of 22·3 months (IQR 16·2-30·9), 449 progression-free survival events were recorded. Median progression-free survival was 17·3 months (95% CI 15·2-20·2) in patients assigned to treatment every 3 weeks, versus 18·3 months (16·8-20·9) in women allocated to the weekly schedule (hazard ratio 0·96, 95% CI 0·80-1·16; p=0·66). FACT-O/TOI scores differed significantly between the two schedules (treatment-by-time interaction p<0·0001); with treatment every 3 weeks, FACT-O/TOI scores worsened at every cycle (weeks 1, 4, and 7), whereas for the weekly schedule, after transient worsening at week 1, FACT-O/TOI scores remained stable. Fewer patients assigned to the weekly group than those allocated treatment every 3 weeks had grade 3-4 neutropenia (167 [42%] of 399 patients vs 200 [50%] of 400 patients), febrile neutropenia (two [0·5%] vs 11 [3%]), grade 3-4 thrombocytopenia (four [1%] vs 27 [7%]), and grade 2 or worse neuropathy (24 [6%] vs 68 [17%]). Three deaths during the study were attributed to chemotherapy; two women died who were allocated treatment every 3 weeks and one death was recorded in the group assigned the weekly regimen. A weekly regimen of carboplatin and paclitaxel might be a reasonable option for first-line treatment of women with advanced ovarian cancer. None.

Quality of life as a primary endpoint in ovarian cancer trials

Multimodal treatment of patients with advanced ovarian cancer consists of radical debulking surgery and a combination of platinum and taxane chemotherapy. Although this approach is highly effective and potentially curative, most women will relapse, which can be treated effectively but is rarely cured. 1 du Bois A Reuss A Pujade-Lauraine E Harter P Ray-Coquard I Pfisterer J Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO). Cancer. 2009; 115: 1234-1244 Crossref PubMed Scopus (1037) Google Scholar In this context, quality of life is an important outcome measure. Unfortunately, few detailed analyses of quality of life have been done in large first-line treatment trials for ovarian cancer: primary publications traditionally focus on efficacy data and, typically, only outline results of quality of life are presented. Detailed description of health-related quality of life could help clinicians and patients with respect to making informed treatment decisions. 2 Luckett T King M Butow P Friedlander M Paris T Assessing health-related quality of life in gynecologic oncology: a systematic review of questionnaires and their ability to detect clinically important differences and change. Int J Gynecol Cancer. 2010; 20: 664-684 Crossref PubMed Scopus (47) Google Scholar Carboplatin plus paclitaxel once a week versus every 3 weeks in patients with advanced ovarian cancer (MITO-7): a randomised, multicentre, open-label, phase 3 trialA weekly regimen of carboplatin and paclitaxel might be a reasonable option for first-line treatment of women with advanced ovarian cancer. Full-Text PDF