Carboplatin致灰鼠内毛细胞损害的扫描电镜观察

本文应用扫描电镜观察了Carboplatin耳中毒引起的内毛细胞表面亚显微结构的改变。发现用药后仅1天，在内毛细胞表面即开始出现球状物，同时伴有个别内毛细胞坏死，注药后3天，大多数内毛细胞的纤毛发生散乱。注药后30天，坏死的内毛细胞处为支持细胞所替代，残存的内毛细胞表面结构可以恢复正常。

Carboplatin对灰鼠前庭系统的影响

本研究目的在于调查一种抗肿瘤药Carboplatin（100m／kg）对灰鼠前庭器官功能与形态的影响。注射Carboplatin后，冷水诱发眼震持续时间明显缩短。急性形态学损害主要发生在Ⅰ型毛细胞的传入神经末梢和胞核。另外，壶腹嵴的形态学损害比球囊斑和椭园囊斑发生早而且更为严重。在囊斑内，微纹区是病变的主要部位。用药后30天，壶腹嵴和囊斑有较多Ⅰ型毛细胞缺失，然而Ⅱ型毛细胞未受明显影响。上述结果表明Carboplatin具有迅速的强烈的前庭毒性作用，Ⅰ型毛细胞和传入神经末梢是主要受损部位。

Nedaplatin/Gemcitabine Versus Carboplatin/Gemcitabine in Treatment of Advanced Non-small Cell Lung Cancer: A Randomized Clinical Trial

Objective： To evaluate the efficacy and safety of nedaplatin/gemcitabine （NG） and carboplatin/gemcitabine （CG） in the management of untreated advanced non-small cell lung cancer （NSCLC）. Methods： Sixty-two patients with previously untreated advanced NSCLC were recruited between June 2006 and November 2007. Subjects were randomly assigned to the NG arm （n=30） and the CG arm （n=32）. Only patients （24 and 25 in the NG and CG arms, respectively） who completed 〉2 chemotherapy cycles were included in the data analysis. The primary outcome measure was the objective response rate （ORR）. The secondary outcome measures included progression-free survival （PFS）, overall survival （OS） and adverse events. Results： There were no statistically significant differences in the efficacy measures （ORR, P=0.305; median PFS, P=0.298, median OS, P=0.961） or in the major adverse events （grade 3/4 neutropenia, P=0.666; grade 3/4 anemia, P=0.263; grade 3/4 thrombocytopenia, P=0.222） between the two treatment arms. However, there was a trend towards higher ORR （37.5% vs. 24.0%）, longer PFS （6.0 vs. 5.0 months）, and less adverse events in the NG arm. Conclusion： NG regimen seems to be superior over CG regimen for advance NSCLS, but further investigation is needed to validate this superiority.

OTOTOXIC EFFECTS OF CARBOPLATIN IN ORGANOTYPIC CULTURES IN CHINCHILLAS AND RATS

Carboplatin, a second-generation platinum chemotherapeutic drug, is considerably less ototoxic than cisplatin. While common laboratory species such as mice, guinea pigs and rats are highly resistant to carboplatin ototoxicity, the chinchilla stands out as highly susceptible. Moreover, carboplatin causes an unusual gradient of cell death in chinchillas. Moderate doses selectively damage type I spiral ganglion neurons (SGN) and inner hair cells (IHC) and the lesion tends to be relatively uniform along the length of the cochlea. Higher doses eventually damage outer hair cells (OHC), but the lesion follows the traditional gradient in which damage is more severe in the base than the apex. While carboplatin ototoxicity has been well documented in adult animals in vivo, little is known about its in vitro toxicity. To elucidate the ototoxic effects of carboplatin in vitro, we prepared cochlear and vestibular organotypic cultures from postnatal day 3 rats and adult chinchillas. Chinchilla cochlear and vestibular cultures were treated with carboplatin concentrations ranging from 50 μM to 10 mM for 48 h. Consistent with in vivo data, carboplatin selectively damaged IHC at low concentrations (50-100 μM). Surprisingly, IHC loss decreased at higher doses and IHC were intact at doses exceeding 500 μM. The mechanisms underlying this nonlinear response are unclear but could be related to a decrease in carboplatin uptake via active transport mechanisms (e.g., copper). Unlike the cochlea, the carboplatin dose-response function increased with dose with the highest dose destroying all chinchilla vestibular hair cells. Cochlear hair cells and auditory nerve fibers in rat cochlear organotypic cultures were unaffected by carboplatin concentrations <10 μM; however, the damage in OHC were more severe than IHC once the dose reached 100 μM. A dose at 500 μM destroyed all the cochlear hair cells, but hair cell loss decreased at high concentrations and nearly all the cochlear hair cells were present at the highest dose, 5 mM. Unlike the nonlinear dose-response seen with cochlear hair cells, rat auditory nerve fiber and spiral ganglion losses increased with doses above 50 μM with the highest dose destroying virtually all SGN. The remarkable species differences seen in vitro suggest that chinchilla IHC and type I SGN posse some unique biological mechanism that makes them especially vulnerable to carboplatin toxicity.

A phaseⅠtrial of an oral subtype-selective histone deacetylase inhibitor,chidamide,in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer

Objective： This phase I study was to evaluate safety, maximum tolerated dose, pharmacokinetics and preliminary antitumor activity of chidamide, a novel subtype-selective histone deacetylase （HDAC） inhibitor, in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer （NSCLC）. Methods： Ten patients received oral chidamide 20, 25, or 30 mg twice per week continuously with paclitaxel （175 mg/m2） and carboplatin [area under the curve （AUC） 5 mg/mL/min] administered in a 3-week cycle. Patients with response and stable disease after four cycles maintained chidamide monotherapy until disease progression or unacceptable toxicity. Blood samples were collected for pharmacoldnetic analysis after the first single oral of chidamide and first combination treatment in cycle 1 from all patients. Results： Two dose-limiting toxicities were recorded in the 30 mg cohort, including thrombocytopenia and prolonged neutropenia in the first cycle. Grade 3/4 neutropenia in any cycle was observed in all patients, but was not associated with significant complications. Other grade 3/4 hematologic toxicities included thrombocytopenia and leucopenia. No significant changes were observed in pharmacokinetic parameters for both chidamide and paclitaxel. One patient in the 20 mg cohort had confirmed partial response （PR）. Two out of 5 patients with brain metastases had intracranial complete remission after 4-cycle treatment. Conclusions： Chidamide combined with paclitaxel and carboplatin was generally tolerated without unanticipated toxicities or clinically relevant pharmacokinetic interactions. The recommended dose for chidamide in this combination was established at 20 mg, and a phase II trial is ongoing with this regimen in patients with advanced NSCLC.

A phase Ⅱ study of gemcitabine and carboplatin combination chemotherapy in gallbladder carcinoma

BACKGROUND: Patients with carcinoma of the gallbladder have advanced, unresectable tumor at the time of presentation and face a dismal prognosis in the absence of a standard palliative chemotherapy regimen. This study was undertaken to evaluate the efficacy and safety of combined chemotherapy of gemcitabine and carboplatin in 20 patients with advanced gallbladder carcinoma. METHODS: The criteria of eligibility included chemonaive patients with unresectable gallbladder cancer, bidimensionaIly measurable disease, Zubrod's performance status≤2, and adequate major organ function. The patients received gemcitabine (1000 mg/m^2) on days 1 and 8, and carboplatin (target AUC of 5.0 mg/ml) on day 1, in a 21-day cycle. CT was used for response assessment. RESULTS: In this group of 20 patients with advanced gallbladder carcinoma 6 were men and 14 women, with a median age of 55 years. The stage of the tumor at presentation was IVB in 14 patients (70%), IVA in 3 (15%) and Ⅲ in 3 (15%). Four patients (21%) achieved a complete response, and 3 (15.7%), a partial response; an overall response rate was 36.7%. The median time to progression of the tumor was 33.8 weeks, and 1-year survival rate of the patients was 43.3%. Anemia of WHO grade Ⅲ or Ⅳ was seen in 2 patients (10%) and 1 patient (5%), respectively. Grade Ⅲ neutropenia and thrombocytopenia were observed in 2 patients (10%) and 1 patient (5%), respectively. CONCLUSION: With mild toxicity, combined chemotherapy of gemcitabine and carhoplatin is effective in the treatment of advanced gallbladder carcinoma.

Association between HER2 status and response to neoadjuvant anthracycline followed by paclitaxel plus carboplatin chemotherapy without trastuzumab in breast cancer

Background： We recently showed HER2-positive breast cancers are less likely to respond to neoadjuvant anthracycline chemotherapy. Here, we investigated whether HER2-positive breast cancers responded to sequential neoadjuvant anthracycline followed by paclitaxel plus carboplatin regimen in the absence of trastuzumab. Methods： Women （n=372） with operable primary breast cancer initially received two cycles of neoadjuvant anthracyclines, the clinical tumor response was assessed, then patients were received four cycles of paelitaxel plus carboplatin regimen. All the patients did not received trastuzumab treatment in the neoadjuvant setting. HER2 status was determined by immunohistochemistry and/or by fluorescence in situ hybridization in core- biopsy breast cancer tissue obtained before the neoadjuvant chemotherapy. Results： Eighteen percent （67/372） of patients achieved a pathologic complete response （pCR） in their breast. HER2-positive tumors had a significant higher pCR rate than HER2-negative tumors （33.0% versus 13.5%, P〈0.001） in this cohort of 372 patients, and positive HER2 status remained an independent favorable predictor of pCR in a multivariate analysis [odds ratio （OR）, 2.26; 95% confidence interval （CI）, 1.18 to 4.36, P=0.015]. Furthermore, patients who responded to initial anthracycline regimens were more likely to respond to paclitaxel plus carboplatin than patients who did not （pCR, 27.2% versus 14.6%, P=0.005）. Patients with HER2-positive tumors exhibited a significant higher pCR rate than did patients with HER2- negative tumors in both anthracycline response group （40.5% versus 20.0%, P=0.025） and anthracycline non-response group （28.3% versus 11.3 %, P=0.002）. Conclusions： Under the circumstance of no trastuzumab treatment, women with HER2-positive cancers derive a large benefit from paclitaxel-carboplatin-based neoadjuvant chemotherapy.

Dose-dense paclitaxel plus carboplatin vs.epirubicin and cyclophosphamide with paclitaxel as adjuvant chemotherapy for high-risk triple-negative breast cancer

Objective:The objective of this open-label,randomized study was to compare dose-dense paclitaxel plus carboplatin(PCdd)with dose-dense epirubicin and cyclophosphamide followed by paclitaxel(ECdd-P)as an adjuvant chemotherapy for early triple-negative breast cancer(TNBC).Methods:We included Chinese patients with high recurrence risk TNBC who underwent primary breast cancer surgery.They were randomly assigned to receive PCdd[paclitaxel 150 mg/m2 on d 1 and carboplatin,the area under the curve,(AUC)=3 on d 2]or ECdd-P(epirubicin 80 mg/m2 divided in 2 d and cyclophosphamide 600 mg/m2 on d 1 for 4 cycles followed by paclitaxel 175 mg/m2 on d 1 for 4 cycles)every 2 weeks with granulocyte colony-stimulating factor(G-CSF)support.The primary endpoint was 3-year disease-free survival(DFS);the secondary endpoints were overall survival(OS)and safety.Results:The intent-to-treat population included 143 patients(70 in the PCdd arm and 73 in the ECdd-P arm).Compared with the ECdd-P arm,the PCdd arm had significantly higher 3-year DFS[93.9%vs.79.1%;hazard ratio(HR)=0.310;95%confidence interval(95%CI),0.137-0.704;log-rank,P=0.005]and OS(98.5%vs.92.9%;HR=0.142;95%CI,0.060-0.825;log-rank,P=0.028).Worse neutropenia(grade 3/4)was found in the ECdd-P than the PCdd arm(47.9%V5.21.4%,P=0.001).Conclusions:PCdd was superior to ECdd-P as an adjuvant chemotherapy for early TNBC with respect to improving the 3-year DFS and OS.PCdd also yielded lower hematological toxicity.Thus,PCdd might be a preferred regimen for early TNBC patients with a high recurrence risk.

Effect of 2-(8-hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid in combination with carboplatin on gastric carcinoma growth in vivo

AIM： To investigate the effects of 2-（8-hydroxy-6- methoxy-l-oxo-lH-2-benzopyran-3-yl） propionic acid （NM-3） alone and in combination with carboplatin on tumor growth and apoptosis in mouse models of human gastric cancer constructed by subcutaneous implantation of histologically intact tumor tissue. METHODS： Human gastric cancer SGC-7901 tissues were implanted into the dorsal subcutis of nude mice. One week after tumors reached to a volume of 50-100 mm3 for around 1 wk, these mice were randomly divided into 8 groups （n = 10）. NM-3 was injected peritoneally at the dose of 10 mg/kg, 20 mg/kg or 40 mg/kg every other day for 5 wk, combined with carboplatin （5 mg/kg） every third day for 4 wk. As controls of combined treatment, another 4 groups of mice were injected with either NM-3 at 10 mg/kg, 20 mg/kg or 40 mg/kg, or with carboplatin alone （5 mg/kg）. The control mice received normal saline. Tumor weight, tumor growth inhibition （TGI）, and intratumoral microvessel density （MVD） were evaluated. Apoptosis of human gastric cancer was detected by TUNEL method and flow o/tometry analysis, respectively. RESULTS： The mean tumor volume （692.40 ± 58.43 mm3, 548.30 ± 66.02 mm3, 382.13 ± 43.52 mm3） after treatment with carboplatin combined NM-3 at the dose of 10 mg/kg, 20 mg/kg or 40 mg/kg was lower than that after treatment with either NM-3 at the dose of 10 mg/kg, 20 mg/kg or 40 mg/kg or with carboplatin alone. Compared with the normal saline group, NM-3 administered at 10 mg/kg, 20 mg/kg or 40 mg/kg significantly reduced the tumor weight in these groups （P 〈 0.05）. Carboplatin used alone at 5 mg/kg showed minimal effects. But NM-3 in combination with carboplatin had greater effects of tumor weight than either NM-3 or carboplatin alone. NM-3 alone at the dose 10 mg/kg or in combination with carboplatin had no obvious effects on body changes. Two mice died of diarrhea in each of the two groups treated with 40 mg/kg NM-3 or with 40 mg/kg NM-3 in combination with carboplatin. A significant increase in apoptosis was observed in the NM-3 treated groups, and the effect was more significant in the groups treated with carboplatin in combination with NM-3 at 10 mg/kg, 20 mg/kg and 40 mg/kg, than in the control group. The induction of apoptosis was positively associated with the dose of NM-3. NM-3 significantly reduced the neomicrovascular formation of gastric cancer. The MVD was lower in the groups treated with NM-3 or with NM-3 in combination with carboplatin than in the group treated with carboplatin or in the normal saline group （P 〈 0.05）. CONCLUSION： The results suggest that the inhibitory effect of NM-3 on gastric cancer growth is mediated through decreased angiogenesis and the increased induction of apoptosis. Furthermore, NM-3 alone at the dose of 10 mg/kg or in combination with carboplatin has no obvious effects on body changes, indicating that NM-3 in combination with carboplatin may be effective in the treatment of gastric cancer. The toxicity of NM-3 needs further studies.

PACLITAXEL PLUS CARBOPLATIN FOR WOMEN WITH ADVANCED BREAST CANCER

Objective To evaluate the efficacy and safety of combination chemotherapy with paclitaxel and carboplatin for advanced breast cancer (ABC). Methods From January 2001 to March 2006, 45 patients with ABC were treated with combination chemotherapy of paclitaxel and carboplatin. Patients received infusion of paclitaxel 175 mg/m2 on day 1 every 3 weeks or 75 mg/m2 on day 1, 8, 15 every 4 weeks. Carboplatin was administrated on day 2 with a dose of area under the time-concentration curve (AUC) being 5. Results The median number of cycles was 3 (range, 2-6). The overall response rate was 62.2%. Median time to progression was 7.0 months (95%CI:5.1-8.9). Median overall survival was 29.0 months (95%CI: 20.1-37.9). One year survival rate was 73.3%. Response rate for first line and second line treatment were 62.1% and 62.5%, respectively. No significant difference in response existed between visceral metastasis and soft tissue metastasis. The main side effects included nausea/vomiting, neurotoxicity, and hematologic toxicities. Grade Ⅲ to Ⅳ adverse events included nausea/vomiting in 2 cases (4.4%), leukopenia in 17 cases (37.8%), and alopecia in 6 cases (13.3%). Conclusion Combination of paclitaxel and carboplatin is active in treatment of ABC with an acceptable toxicity profile.

Gas-blasting nanocapsules to accelerate carboplatin lysosome release and nucleus delivery for prostate cancer treatment

To improve therapeutic effect and reduce severely side effects of carboplatin(CBP),the gas-generating nanocapsules were developed to accelerate CBP lysosome release and nucleus delivery.CBP/SB-NC was prepared by co-loading CBP and NaHCO 3(SB)in nanocapsules using w/o/w emulsification solvent evaporation.They exhibited vesicle-like spherical morphology,uniform particle size and negative zeta potential.Reaching the tumor site with a relatively high concentration is the first step for CBP delivery and the results showed that CBP/SB-NC could effectively increase drug accumulation at tumor site.After that,the drug delivery carriers need to be internalized into tumor cells and the in vitro cellular uptake ability results showed CBP/SB-NC could be internalized into RM-1 cells more efficient than CBP solution.After internalized by RM-1 cells,the gas-blasting release process was tested in acid environment.It was demonstrated that 5 mg/ml NaHCO 3 was optimal to achieve pH-responsive gas-blasting release.In vitro release results showed that CBP significantly rapid release in acid environment(pH 5.0)compared to neutral pH(pH 7.4)(P<0.05).Meanwhile,TEM and the change of the concentration of H+results exhibited that the explosion of CBP/SB 5-NC was more easily happened in lysosome acid environment(pH 5.0).The blasting release can accelerate CBP lysosome release to cytoplasm.Furthermore,the nucleus delivery results showed CBP/SB 5-NC can promote pH-triggered rapid nucleus delivery.And the results of Pt-DNA adduct assay showed that the binding efficiency between CBP and DNA of CBP/SB 5-NC was higher than CBP solution.At last,in vitro and in vivo anti-tumor efficacy proved that CBP/SB 5-NC could enhance anti-tumor activity for prostate cancer therapy.CBP/SB 5-NC also showed superior safety in vitro and in vivo by hemolysis assay and histopathological study.All of the results demonstrate that CBP/SB 5-NC would be an efficient gas-blasting release formulation to enhance prostate cancer treatment.

Determination of Carboplatin Dose by Area Under the Curve in Combination Chemotherapy for Senile Non-small Cell Lung Cancer

To preliminarily determine the appropriate dosage of carboplatin （CBP） at AUC of 5 mg-M1^-1·min^-1 in the combination chemotherapy for Chinese senile patients with non-small cell lung cancer （NSCLC）. Thirty-five Chinese senile patients with NSCLC in advanced stage （Ⅲ/Ⅳ） were given 96 cycles of combination chemotherapy. Chemotherapy schedules included Taxol＋CBP, Gemzar＋CBP and NVB＋CBE The dose of CBP was at 5 mg.mL^-1·min^-1 of area under the concentration-time curve （AUC）. Side effects and quality of life were observed before and after the chemotherapy. Myelosuppression was severe and commonly observed. Grade 3/4 of granulocytopenia was found in 47.9% （46/96） of the patients and grade 3/4 of thrombocytopenia was noted in 28.1% （27/96） of the subjects. However, other side effects were slight. The mean score of quality of life （QOL）, according to the criteria of QOL for Chinese cancer patients had reduced 6.8. At 5 mg.mL^-1·min^-1 by AUC, the hematological toxicity of CBP was severe and it had some negative effects on the QOL. The administration of CBP at 5 mg.mL^-1·min^-1 by AUC may be too high for Chinese senile patients with non-small cell lung cancer.

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.

Comparison of efficacy and toxicity between gemcitabine plus cisplatin and plus carboplatin in first-line treatment of advanced non-small cell lung cancer

Objective: To compare the efficacy and toxicity between gemcitabine plus cisplatin and plus carboplatin in first-line treatment of advanced non-small cell lung cancer (NSCLC). Methods: Gemcitabine 1000 mg/m2 iv, d1, 8; cisplatin 75 mg/m2 iv, d1, or 25 mg/m2 iv, d1-3; carboplatin AUC = 5 iv, d1; repeated every 21 days. Results: All 76 cases were available for objective response. Gemcitabine + cisplatin (GCis) group: among 33 cases, CR 1 case, PR 13 cases, MR 3 cases, SD 7 cases, PD 9 cases, response rate, disease control rate, time to progress (TTP), median survival time (MST) and 1-, 2-year survival rates were 42.42% (14/33), 72.73% (24/33), 5 months, 14 months and 66.67% (22/33), 12.12% (4/33), respectively; Gemcitabine + carboplatin (GCarb) group: among 43 cases, PR 13 cases, MR 11 cases, SD 7 cases, PD 12 cases, the results while comparing with those of GCis group were 30.23% (13/43), 72.09% (31/43), 4 months, 11 months and 48.84% (21/43), 2.33% (1/43), respectively. Among them, only MST between the two groups had significant statistic difference (χ2 = 2.45, P = 0.017). Mild to modest myelo-suppression as well as nausea and vomiting were observed. Conclusion: Both GCis and GCarb regimens had active and well-tolerated toxicity for advanced NSCLC. Cisplatin-based chemotherapy yields a substantial effective advantage over carboplatin-based regimens. Therefore, carboplatin and cisplatin are not equal-active and that cisplatin-based doublet regimens should remain the standard first-line therapy for patients with advanced NSCLC with good performance status.

Effects of CMNa combined with paclitaxel and carboplatin on elevated CA125 levels in post-operation advanced ovarian cancer patients

Objective： To investigate the effects of CMNa combined with paclitaxel and carboplatin on elevated CA125 levels in post-operation advanced ovarian cancer patients. Methods： The effects of CMNa combined with paclitaxel and carboplatin on elevated CA125 levels in 25 post-operation advanced ovarian cancer patients were retrospectively analyzed and com- pared with those in 20 control cases. Results： After 1 cycle of chemotherapy, CA125 levels had decreasing trend compared with control, but had no statistical significance. While after two cycles of chemotherapy, CA125 levels decreased more rapidly compared with those in control. Side effects in two groups were alike. Conclusion： CMNa combined with paclitaxel and car- boplaline has a stronger effect on the decrease of elevated CA125 levels than paclitaxel and carboplatin have in the treatment of post-operation advanced ovarian cancer, which indicates that CMNa has chemo-sensitizing effects on chemotherapy of paclitaxel and carboplatin.

Three Weeks Carboplatin/Paclitaxel versus Weekly Regimen in Egyptian Women Cohort Treated for Ovarian Carcinoma

Introduction: Epithelial Ovarian Carcinoma (EOC) comprises the vast majority (almost 90%) of ovarian carcinomas. Chemotherapy is the main treatment in ovarian cancers. The standard of care in the chemotherapeutic is the combination of a platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel). Studies were done to determine whether this combination to be given weekly or every 3 weeks. Patient and Method: Inclusion criteria: 1) Female patients between the ages of 17 - 78 years. 2) Baseline hematological, renal and liver laboratory profiles were within accepted ranges. 3) Performance status of the patients was 0-II. 4) Patients were pathologically proven ovarian cancer. 5) A follow-up period for at least 6 months was required. Exclusion criteria: 1) Patients who had double malignancy were excluded. 2) Performance status more than II. 3) Other comorbidity. Results: We reviewed 69 female patients with EOC, with 60% received every three weeks regimen. Mean age was 53.22 years. At a median follow up of 45.9 months, there was no significant different between the two protocols in terms of mean PFS, 62.35 months (95% CI: 50.08 - 74.63 months) for the three-weekly cohort, and 69.25 months (95% CI: 55.24 - 83.26 months) for weekly protocol (p = 0.613). The three weekly regimen patients had a higher incidence of hospital admission (40% vs 18.5% for the weekly protocol patients), but it didn’t reach a statistical significance (p = 0.063). The three weekly protocol had a significantly higher incidence of causing a neutropenic fever (p = 0.003). Conclusion: In our cohort of Egyptian women with EOC, no significant difference in PFS was found when compared the weekly Carboplatin/paclitaxel when compared to the classic three weeks, although the weekly protocol may be causing less febrile neutropenia and fewer hospital admissions.

Preoperative Conformal Radiotherapy Concurrently with Paclitaxel/Carboplatin in Gastric Cancer

Background and objectives: Surgery is the primary therapy for localized gastric cancer, but even with the best results only 40% 5-year survival can be achieved with the use of postoperative adjuvant chemoradiotherapy. Preoperative therapy might help increase the R0 resection rate, which is an independent predictor of 5-year OS. Our study hypothesized that the concurrent combination of carboplatin-paclitaxel with radiation therapy would result in a pathological CR rate, which will be in turn associated with OAS and DFS benefits. Patients and methods: prospective phase II study included 32 patients with locally advanced gastric adenocarcinoma including gastroesophageal junction who received a combination of neoadjuvant conformal radiotherapy concurrently with carboplatin-paclitaxel followed by surgery. Results: Pathological CR and R0 resection rates were 18.8% and 75% respectively. With a median follow up of 24 months, 2 years disease-free survival was 28.1% and overall survival was 51.3%. The regimen was tolerated with neither grade 4 toxicities nor deaths. Conclusion: Neoadjuvant radiotherapy concomitant with carboplatin-paclitaxel chemotherapy is a well-tolerated approach for patients with locally advanced gastric adenocarcinoma resulting in significant pathological CR and R0 resection margins as reflected by the good DFS and OS.

EFFECT OF NEOADJUVANT CHEMOTHERAPY USING PACLITAXEL COMBINED WITH CARBOPLATIN ON ADVANCED NON-SMALL CELL LUNG CANCER

Objeetive： To assess the therapeutic effectiveness of preoperative neoadjuvant chemotherapy using a combination of paclitaxel and carboplatin on local advanced non-small cell lung cancer （NSCLC）. Methods： Twenty-five patients with advanced NSCLC were treated with paclitaxel and carboplatin for 2 to 4 cycles before undergoing tumor resection and then postoperative chemotherapy/radiotherapy therapy for 2 to 4 cycles. Results： Following neoadjuvant chemotherapy, the most prominent side-effect was bone marrow restraint. The overall response rate of preoperative chemotherapy was 56%. The mean survival time was 26.5 months, with 1-, 2- and 5-year survival rates of 55%, 25%, and 16%, respectively. All NSCLC patients survived the perioperative period. Conclusion： Preoperative neoadjuvant chemotherapy combining paclitaxel and carboplatin produced minimal side-effect while increasing the probability that advanced NSCLC patients would be able to undergo surgery thus improving their prognosis.

Pegylated liposomal doxorubicin/carboplatin combination in ovarian cancer, progressing on single-agent pegylated liposomal doxorubicin

AIM: To assess the efficacy and safety of the combination of pegylated liposomal doxorubicin(PLD) and carboplatin in patients with recurrent epithelial ovarian carcinoma(ROC), following disease progression on single agent PLD. METHODS: An analysis of the medical records of 10 patients with ROC, treated in our institution with a combination of PLD and carboplatin following progression on single-agent PLD therapy was performed. The median age was 59.1 years(range, 45 to 77 years). All diagnoses were histological-proven. Eight of the 10 patients were platinum-resistant. Following disease progression on single-agent PLD treatment, carboplatin area under the curve(AUC)-5 was added to PLD in all 10 patients. In order to assess disease status, Ca-125 was assessed before each PLD/carboplatin treatment. Relative changes in Ca-125 values were calculated, and response defined as a greater than 50% reduction in Ca-125 from baseline. Radiographic studies were reevaluated and responses to therapy based on com-puter tomography(CT) scans carried out on a regular basis every 2-3 mo in each patient. Statistical analysis was performed using SPSS(V19).RESULTS: A median of 10 cycles(range, 2-26) of the carboplatin-PLD combination was given. Of the 10 treated patients, 6 had > 50% reduction in Ca-125 levels from baseline, 4 of these had a partial response according to Response Evaluation Criteria in Solid Tumors(RECIST) criteria, and the other 2 patients had no measurable disease. In a further 2 patients with a best response of disease stabilization and < 50% reduction of Ca-125 levels, one had progression of disease after 26 cycles, and the second progressed with brain metastases following 12 cycles. Seven of the eight patients who were platinum-resistant showed evidence of clinical benefit on carboplatin-PLD combination therapy; 5 of these had > 50% reduction in Ca-125 level, 4 also showed a partial response on CT scan. The treatment was generally well-tolerated by the patients. CONCLUSION: Addition of carboplatin to PLD, after disease progression on single-agent PLD therapy, is both effective and safe in patients with ROC, even in those with Platinum-resistant disease.

Cisplatin比Carboplatin更能有效治疗非小细胞性肺癌

据美国BIOCOMPARE科技新闻网（2007／6／15）报道，一篇发表于6月6日的《国立癌症研究院期刊》（Journal of the National Cancer Institute）研究报告称，研究人员发现有些末期的非小细胞性肺癌（NSCLC）患者接受cisplatin治疗的存活率较carboplatin高。