Toxicity Of Carboplatin Research Articles

Equivalence of cisplatin and carboplatin-based chemoradiation for locally advanced squamous cell carcinoma of the head and neck: A matched-pair analysis

Carboplatin can be substituted for cisplatin in concomitant chemoradiation (CRT) for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) when the latter is contraindicated. This matched-pair study aimed to compare the efficacy and acute toxicity of carboplatin and cisplatin. Patients treated with 2 cycles of concomitant carboplatin-based CRT were matched to patients treated with 2 cycles of cisplatin. Matching criteria included age, tumour site, stage, smoking status and use of induction chemotherapy. Radiation was delivered using conformal techniques. Data on weekly acute toxicity throughout CRT was compared using the chi-squared test for proportions. Kaplan Meier statistics described time to local relapse, distant relapse and overall survival, the log-rank test was used to compare 3-year survival outcomes. Sixty-five patients who received carboplatin were matched to 65 who received cisplatin. Significant differences in toxicity included increased emesis with cisplatin and more anaemia and thrombocytopenia with carboplatin. There was no significant difference in 3-year locoregional control (87% vs. 79%, p=0.54), freedom from distant metastases (88% vs. 85%, p=0.79) and overall survival (59% vs. 68%, p=0.24) between the carboplatin and cisplatin cohorts, respectively. When cisplatin is contraindicated, carboplatin-based CRT yields equivalent treatment outcomes in patients with LASCCHN.

The effects of taurolidine alone and in combination with doxorubicin or carboplatin in canine osteosarcoma in vitro

BackgroundOsteosarcoma (OS) affects over 8000 dogs/year in the United States. The disease usually arises in the appendicular skeleton and metastasizes to the lung. Dogs with localized appendicular disease benefit from limb amputation and chemotherapy but most die within 6–12 months despite these treatments. Taurolidine, a derivative of taurine, has anti-tumor and anti-angiogenic effects against a variety of cancers. The following in vitro studies tested taurolidine as a candidate for adjuvant therapy for canine OS. Tests for p53 protein status and caspase activity were used to elucidate mechanisms of taurolidine-induced cell death.ResultsTaurolidine was cytotoxic to osteosarcoma cells and increased the toxicity of doxorubicin and carboplatin in vitro. Apoptosis was greatly induced in cells exposed to 125 μM taurolidine and less so in cells exposed to 250 μM taurolidine. Taurolidine cytotoxicity appeared caspase-dependent in one cell line; with apparent mutant p53 protein. This cell line was the most sensitive to single agent taurolidine treatment and had a taurolidine-dependent reduction in accumulated p53 protein suggesting taurolidine’s effects may depend on the functional status of p53 in canine OS.ConclusionTaurolidine’s cytotoxic effect appears dependent on cell specific factors which may be explained, in part, by the functional status of p53. Taurolidine initiates apoptosis in canine OS cells and this occurs to a greater extent at lower concentrations. Mechanisms of cell death induced by higher concentrations were not elucidated here. Taurolidine combined with doxorubicin or carboplatin can increase the toxicity of these chemotherapy drugs and warrants further investigation in dogs with osteosarcoma.

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.

Mutagenic Effects of Carboplatin on Somatic Cells of Male Albino Mice

Carboplatin is one of the anticancer drugs used in chemotherapy for cancer patients. Cytogenetic effects were evaluated by employing bone marrow micronucleus test, one of the short-term tests that adopted in such studies. Micronucleus test was used by injecting the mice with the three doses for five consecutive days into the intraperitoneal injection. Toxicity of carboplatin was observed in stimulates the production of micronucleus in polychromatic erythrocytes of bone marrow of treated mice. A dose-response relationship was observed giving evidence that carboplatin is positive clastogene.

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 10mM for 48h. 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, 5mM. 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.

Hyperglycemia regulates MDR-1, drug accumulation and ROS levels causing increased toxicity of carboplatin and 5-fluorouracil in MCF-7 cells

There is constant increase in number of diabetic cases thereby giving it status of a serious epidemic. Diabetes increases the risk of occurrence of several cancers including breast cancer and may also have a serious impact on the outcome of cancer treatment. In the present study we investigated effect of hyperglycemia on cytotoxic efficacy of carboplatin and 5-fluorouracil in MCF-7 cells. MCF-7 cells were grown in 5.5 or 25 mM glucose chronically. We show that hyperglycemia favors proliferation of MCF-7 cells and increases expression of cell cycle regulatory proteins cyclin E and cdk-2. Hyperglycemia enhances cytotoxicity of carboplatin and 5-fluorouracil in MCF-7 cells by approximately 30% and decreases their IC50 by 1.5- and 1.3-folds, respectively. Hyperglycemia reduces expression of P-glycoprotein and promotes cell killing by increasing drug accumulation. Treatment with 40 µM verapamil, an inhibitor of P-gp activity specifically increases killing of MCF-7 cells cultured in 5.5 mM glucose. Further, this effect is synergized by elevated reactive oxygen species and treatment with N-Acetylcysteine, an inhibitor of ROS, increases survival by 30 and 18% in carboplatin- and 5-fluorouracil-treated cells cultured in high glucose, respectively. Cytotoxicity of these drugs is associated with reduced activation of Akt and decreased transcriptional activation of NF-κB. In conclusion, hyperglycemia potentiates cytotoxicity of drugs by reducing P-gp expression and, increased ROS levels may partially or completely contribute to enhanced toxicity.

Effect of Age on Systemic Exposure and Haematological Toxicity of Carboplatin in Advanced Non-Small Cell Lung Cancer Patients

The aim of this study was to evaluate systemic exposure to carboplatin and its haematological toxicity in patients with advanced non-small cell lung cancer both older and younger than 70 years when the target area under the curve (AUC) in elderly patients was reduced by 20%. For this purpose, a population pharmacokinetic model was developed and the haematological toxicity of the drug was assessed. A total of 33 patients received carboplatin on day 1 and gemcitabine (1250 mg/m(2) ) on days 1 and 8. This schedule was repeated every 21 days. The Calvert-Crokcoft-Gault formula was employed to calculate a dose of carboplatin with a target AUC of 5 mg/min./mL in patients under 70 years and 4 mg/min./mL in patients aged 70 or older. The data of 24 patients were treated for population modelling performed with the nonmem (University of California, San Francisco, CA, USA) approach. Haematological toxicity was evaluated for all 33 patients enrolled in the study. The carboplatin systemic exposure measured by the AUC (mg/min./mL) was 5.98 (5.45; 6.51) and 5.36 (5.02; 5.69) for the younger patients and older groups, respectively. No significant differences were observed between the two groups with respect to rates of grade 3+ anaemia, neutropenia or thrombocytopenia. In clinical practice, a target AUC of 4 mg/min./mL carboplatin is applied to patients aged 70 and over, but the actual systemic exposure to the drug is higher. This supports a target AUC of 4 mg/min./mL carboplatin for patients older than 70 years when the dose is calculated by means of the Calvert-Crokcoft-Gault formula.

Carboplatin Dosing in Ovarian Cancer

Carboplatin is one of the most effective chemotherapeutic drugs for the treatment of ovarian cancer. It has simple pharmacokinetics and a predictable toxicity profile. The dose can be calculated effectively based on a patient's renal function as defined by the glomerular filtration rate (GFR). The measurement of the GFR is best done using radioisotopes, but this is expensive and not widely available, so many centers use equations to estimate GFR based on serum creatinine and other easily measured data. Recent changes in the measurement of serum creatinine, and a move toward isotope dilution mass spectrometry standardized values, have highlighted the difficulty in safely and effectively calculating doses of carboplatin in patients with ovarian cancer. We have evaluated the currently available evidence for the most common methods of estimating and measuring GFR. We explored the problems and pitfalls with using each of these methods or equations and examined the effects of small changes in clinical parameters and the effect on carboplatin dose. Previous studies evaluating carboplatin's toxicity and efficacy used various different methods of GFR estimation and older methods of creatinine measurement. These may not translate to use with newer laboratory methods and may result in higher delivered doses than anticipated. The lack of consistency in carboplatin dosing, and changing creatinine values are a cause for concern if patient toxicity is a possible outcome. The need for new studies using new standard methods that can be widely used are urgently required to provide clarity in this area.

Second-line chemotherapy with docetaxel and carboplatin in paclitaxel and platinum-pretreated ovarian, fallopian tube, and peritoneal cancer

We retrospectively evaluated the efficacy and toxicity of docetaxel and carboplatin in patients with platinum and paclitaxel-pretreated recurrent ovarian, fallopian tube, and peritoneal cancer. Forty-two women (38 with ovarian cancer, 1 with fallopian tube cancer, 3 with peritoneal cancer) whose cancer had progressed within 12 months of their last treatment with both a platinum agent and paclitaxel were treated with docetaxel (70 mg/m(2), day 1) and carboplatin (area under the curve of 4-6, day 1). Thirty-four patients had measurable disease. The objective response rate was 23% within 0-6 months of the progression-free interval, 50% within 6-12 months, and 32% (11 of 34 patients) for both groups. The median time to tumor progression was 28, 49, 34 weeks, and the median overall survival time was 94, 224, 111 weeks, respectively. The most common toxicity was grade 3/4 neutropenia (98% of patients), with 15 episodes (8.4% of courses) of neutropenic fever. The main nonhematologic toxicity was hypersensitivity; 7 patients (17%) required discontinuation of the therapy. The results of our study indicate that the combination of docetaxel and carboplatin is effective against recurrent ovarian, fallopian tube, and peritoneal cancer with progression-free interval of 6-12 months from previous treatment by paclitaxel and platinum. On the other hand, single-agent chemotherapy would be better than this regimen considering its low response rate and severe hematological toxicity for patients with progression-free interval less than 6 months.

Cisplatine ou carboplatine, telle est la question

Platine-based chemotherapy agents are major drugs in oncology and are currently used in most solid malignancies. Of these, cisplatin has been the most widely used over past years. Its efficacy and toxicity have been both well documented in the literature. Carboplatin has a rather different toxicity profile and seems to be better tolerated than cisplatin. This might potentially impact on quality of life. Carboplatin has been assessed for treatment of most malignancies in which cisplatin has demonstrated its efficacy. This paper aims at reviewing and comparing the current indications in terms of efficacy and toxicity of cisplatin and carboplatin. Although cisplatin has demonstrated its superiority over carboplatin for treatment of lung cancers and germ-cell tumors, the tolerance of carboplatin is better than that of cisplatin. This might be taken into account for patients treated with non-curative attempt. Further studies should compare both chemotherapy agents for quality of life. Of course, carboplatin remains widely used for patients who are contra-indicated for cisplatin.

Carboplatin: a new cause of severe type B lactic acidosis secondary to mitochondrial DNA damage

In adults, type B lactic acidosis is rare and generally associated with a toxin, particularly metformin or antiretroviral nucleosides analogues. We report a case of lactic acidosis caused by carboplatin in a 50-year-old woman suffering from primary peritoneal carcinoma. She was admitted for severe lactic acidosis (pH 6.77, lactate 19 mmol/L) associated with multiple organ failure (PaO₂/FiO₂ 96, creatinine 231 μmol/L, aspartate aminotransferase > 25,000 UI, factor V 13%) occurring during the sixth carboplatin cycle. In the absence of sepsis, internal bleeding, alcohol poisoning, or other causes of lactic acidosis, the hypothesis of mitochondrial DNA (mtDNA) damage secondary to carboplatin and subsequent mitochondrial dysfunction leading to increase in glycolysis and lactic acidosis was suspected. L-Carnitine therapy associated with aggressive intensive care support led to a progressive improvement (pH 7.29, bicarbonate 24 mmol/L, lactate 7.8 mmol/L), but life support was withdrawn on day 7 because of peritoneal relapse. A respiratory chain dysfunction of enzyme activities encoded by mtDNA and multiple mtDNA deletions were found in muscle and liver tissue. It is generally accepted that carboplatin toxicity results in bone marrow suppression, renal dysfunction, or neurotoxicity and that platinating agents have no direct mitochondrial effect. However, although very unusual, emergency physicians must be aware that carboplatin can cause mitochondrial toxicity and trigger lactic acidosis.

Factors for Hematopoietic Toxicity of Carboplatin: Refining the Targeting of Carboplatin Systemic Exposure

Area under the curve (AUC) dosing is routinely carried out for carboplatin, but the chosen target AUC values remain largely empirical. This multicenter pharmacokinetic-pharmacodynamic (PK-PD) study was performed to determine the covariates involved in the interindividual variability of carboplatin hematotoxicity that should be considered when choosing individual target AUCs. Three hundred eighty-three patients received carboplatin as part of established regimens. A semi-physiologic population PK-PD model was applied to describe separately the time course of absolute neutrophil and platelet counts using NONMEM software. The plasma ultrafiltrable carboplatin concentration (C(Carbo)) was assumed to inhibit the proliferation of blood cell precursors through a linear model: drug effect = slope × C(Carbo). The slope corresponds to the patients' sensitivity to carboplatin hematotoxicity. The relationships between the patients' sensitivity to the neutropenic or thrombopenic effects of carboplatin and various covariates, including associated chemotherapies, demographic, biologic, and pharmacogenetic data, were studied. The sensitivity of carboplatin-induced thrombocytopenia decreased in the case of concomitant paclitaxel chemotherapy (slope decreased by 24%), whereas it increased with coadministration of etoposide and gemcitabine (slope increased by 45% and 133%, respectively). For neutropenia, the sensitivity increased when carboplatin was combined with other cytotoxics (slope increased by 76%). This study provides useful information to clinicians to better estimate the hematopoietic toxicity of carboplatin and thus choose more rationally carboplatin target AUCs as a function of pretreatment or concomitantly administered chemotherapies. For example, an AUC of 5 mg/mL · min is associated with a risk of grade 3 or 4 thrombocytopenia of 2% in combination with paclitaxel versus 38% with gemcitabine in a non-pretreated patient.

Treatment With Bevacizumab Plus Carboplatin for Recurrent Malignant Glioma

To estimate overall survival (OS), progression-free survival (PFS), imaging responses, and toxicities of bevacizumab plus carboplatin for the treatment of recurrent malignant glioma. The secondary objective was to estimate the agreement between postcontrast T1-weighted and T2-weighted magnetic resonance imaging. A retrospective analysis of 9 patients who received bevacizumab (10 mg/kg intravenously) and carboplatin (AUC 5 intravenously) for recurrent malignant glioma (World Health Organization grades III and IV) is presented. Eight of 9 patients received this regimen at first recurrence. The median age and Karnofsky performance score were 51 years and 70, respectively. For the 5 patients with grade III gliomas, the median PFS was 126 days, whereas median OS was not attained at 517 days of follow-up. Six-month PFS was 40%, whereas 6-month OS was 60%. For the 4 patients with grade IV gliomas, the median PFS was 216 days, whereas the median OS was not attained at 482 days of follow-up. Six-month PFS was 50%, whereas 6-month OS was 75%. The agreement between contrast-enhanced T1-weighted and T2-weighted images to determine recurrence was moderate (kappa=0.5714). Three patients had grade 3 and 4 toxicities including hyponatremia and thrombocytopenia. Patients who received the combination of bevacizumab plus carboplatin for recurrent malignant glioma had reasonable PFS, OS, and toxicities. The median OS in our series is promising at well over 1 year. Agreement between postcontrast T1- and T2-weighted images is only moderate in the context of bevacizumab therapy.

Phase II Evaluation of Paclitaxel and Carboplatin in the Treatment of Carcinosarcoma of the Uterus: A Gynecologic Oncology Group Study

Platinum and taxane compounds have demonstrated activity in uterine carcinosarcoma (malignant mixed Mullerian tumor). Ifosfamide plus paclitaxel is the regimen with established superiority based on a randomized phase III trial conducted through the Gynecologic Oncology Group. However, the toxicity, multiday schedule, and limited activity of this regimen support further development of novel regimens. Our primary objective was to estimate the antitumor activity and toxicity of paclitaxel plus carboplatin in patients with uterine carcinosarcomas. Eligible patients had advanced stage (III or IV), persistent or recurrent measurable disease, and no prior chemotherapy. Patients received paclitaxel at 175 mg/m(2) intravenously (IV) over 3 hours plus carboplatin (area under the serum concentration-time curve = 6) IV over 30 minutes every 3 weeks until disease progression or until adverse effects occurred. Common Terminology Criteria for Adverse Events v3.0 was used to grade adverse events. Fifty-five patients were entered onto the study with nine being excluded from analysis, leaving 46 evaluable for analysis. Treatment was well tolerated with expected hematologic toxicity and minimal nonhematologic grade 4 toxicity (one cardiovascular and two pain) with 59% of patients completing six or more cycles of chemotherapy. The proportions of patients with confirmed complete and partial responses were 13% and 41%, respectively, resulting in a total overall response rate of 54% (95% CI, 37% to 67%). Paclitaxel plus carboplatin demonstrates antitumor activity against uterine carcinosarcoma with acceptable toxicity and warrants further evaluation in phase III randomized trials.

Combination of gemcitabine and carboplatin chemotherapy for recurrent nasopharyngeal carcinoma.

e16006 Background: Although appropriate radiotherapy and combined treatments are widely used for the patients with primary nasopharyngeal carcinoma (NPC), regional or metastatic recurrence rates are still high. This study evaluated the efficacy and toxicity of combination gemcitabine plus carboplatin (GC) chemotherapy in recurrent nasopharyngeal carcinoma (NPC). Methods: Patients with recurrent NPC who have received previous cisplatinum based chemotherapy combined with radiation therapy were eligible for this study. Patients received GC combination: gemcitabine 1,250 mg/m2; days 1, and 8; carboplatin AUC 4 on day 1. Cycles were repeated every 28 days until progression or unacceptable toxicity. Primary endpoint was response rate. Results: 25 patients were enrolled (20 males and 5 females). Median age was 46.5 years. Majority of patients (20) had metastatic disease. 63% of patients have received one previous line of treatment. There were 8 partial responses (32%), 9 stable diseases (36%), and 8 progressive ...

Akt inhibitor enhances apoptotic effect of carboplatin on human epithelial ovarian carcinoma cell lines

Carboplatin and Akt inhibitor have been shown to induce apoptosis in cancer cells. However, the combined effect of Akt inhibitor on the apoptotic effect of carboplatin in epithelial ovarian cancer cells remains uncertain. In the respect of the induction of cell death signaling pathways, we assessed the combined effect of Akt inhibitor on the carboplatin toxicity in the human epithelial ovarian carcinoma cell lines OVCAR-3 and SK-OV-3. Carboplatin and Akt inhibitor induced nuclear damage, decreased Bid and Bcl-2 protein levels, induced cytochrome c release, activated caspase-3 and increased tumor suppressor p53 levels. Carboplatin increased in Bax levels, whereas Akt inhibitor decreased Bax levels. Akt inhibitor enhanced the carboplatin-induced apoptosis-related protein activation and cell death. Combination of carboplatin and Akt inhibitor-induced cell viability loss was reduced by selective inhibitors of caspase-8, -9 and -3. The results suggest that Akt inhibitor may enhance a carboplatin toxicity against ovarian carcinoma cell lines by increasing activation of the caspase-8 and Bid pathway as well as activation of the mitochondria-mediated apoptotic pathway, leading to mitochondrial cytochrome c release and subsequent caspase-3 activation. Combination of carboplatin and Akt inhibitor may provide a therapeutic benefit against ovarian adenocarcinoma.

The feasibility of adjuvant carboplatin and docetaxel in patients with curatively resected locally advanced non-small cell lung cancer

Background Adjuvant cisplatin-based chemotherapy benefits selected patients with stages II and III non-small cell lung cancer (NSCLC). However, carboplatin being tolerated better than cisplatin, carboplatin-based adjuvant therapy may have better chemotherapy compliance. This study aimed to investigate the feasibility and toxicity of adjuvant carboplatin and docetaxel in patients with completely resected locally advanced NSCLC. Methods Eighty patients with completely resected locally advanced NSCLC were enrolled in this trial. Adjuvant chemotherapy was initiated between 1 and 4 weeks after surgery, and consisted of four cycles of carboplatin (AUC = 5), and docetaxel (Taxotere, 75 mg/m 2) every 3 weeks, after which patients received prophylactic G-CSF supportive therapy. Results Patient demographics were: Median age 55 years (range 34–73): gender ratio was 56.3% male/43.7% female: 72.5% of the patients were at stage IIIA and 27.5% were at stage IIIB. The two most common histologies were adenocarcinoma (62.5%) and squamous cell carcinoma (17.5%). Sixty-six patients (82.5%) received four cycles of therapy over a 12-week period. Fourteen patients (17.5%) did not complete therapy due to: patient refusal ( n = 12), severe adverse events ( n = 1) and bone metastases during chemotherapy ( n = 1). No treatment related deaths were observed and the primary adverse events were hematologic toxicity, alopecia, fatigue and gastointestinal reaction (nausea, vomiting and diarrhea). Conclusion Combination therapy with carboplatin and docetaxel with the use of G-CSF supportive therapy has an acceptable toxicity profile such that the majority of patients completed four cycles of therapy in 12 weeks.

P61 Feasibility, efficacy and toxicity of carboplatin and paclitaxel as a first-line treatment in elderly patients with ovarian cancer

P61 Feasibility, efficacy and toxicity of carboplatin and paclitaxel as a first-line treatment in elderly patients with ovarian cancer

Demographic and Clinical Factors Related to Carboplatin Toxicity

01 Clinical Lung Cancer, Vol. 10, No. 5, E5, 2009; DOI: 10.3816/CLC.2009.n.054 Demographic and Clinical Factors Related to Carboplatin Toxicity Sanjay J. Ayirookuzhi, Jerry McLarty, Richard P. Mansour, Glenn M. Mills LSU Health Sciences Center, Division of Hematology-Oncology/Feist-Weiller Cancer Center, Shreveport, LA Background: Carboplatin is a commonly used drug in stage III/IV non–small-cell lung cancer (NSCLC). Myelosuppression is a common toxicity of carboplatin, and this study aimed to assess the relationship between different demographic and descriptive factors and myelosuppression. Patients and Methods: Data from patients with stage III and IV NSCLC seen between January 1, 1999, and December 31, 2007, were analyzed. Patients who received concurrent radiation, had died before the first cycle was completed, or who had missing laboratory values were excluded. Only the first cycle of the carboplatin-based regimen was used for analysis with nadir platelets, hemoglobin, and white blood cell counts (WBCs) used as endpoints. SPSS software was used for statistical analysis including Pearson correlation, analysis of covariance (ANCOVA), independent t tests, and multivariate linear regression models. Results: Of the 216 patients initially abstracted for analysis, only 132 patients qualified for analysis. Demographically, 71 were Caucasian, and the rest were African-American, while 92 were male. The t test to indicate whether nadirs were different by stage were significant for platelets (P = .015) and WBC (P < .0001) but not hemoglobin. t test for race was significant for nadir platelets (P = .008) and hemoglobin (P = .004) but not for nadir WBC. ANCOVA for nadir platelets was significantly related to baseline platelet levels (P < .0001), stage (P = .012) and approached significance for stage with sex (P = .054). ANCOVA performed for nadir hemoglobin was significantly related to race (P = .015), while ANCOVA for nadir WBC was statistically significantly related to BSA (P = .026), baseline WBC count (P < .000), race (P = .017), and stage at diagnosis (P = .045). Carboplatin dose was not found to be statistically significantly related to nadir platelet, WBC, or hemoglobin in these models. Conclusion: Carboplatin is a myelosuppressive drug, and a number of factors are related to its toxicity. Meeting Abstracts Abstracts From: The 10th International Lung Cancer Congress June 17-20, 2009; Kohala Coast, HIs From: The 10th International Lung Cancer Congress June 17-20, 2009; Kohala Coast, HI Program Directors: David R. Gandara, MD; Roy S. Herbst, MD, PhD Clinical Lung Cancer September 2009 | E5 Available Online at www.cigjournals.com

A pilot study of carboplatin and mitoxantrone in blast crisis of chronic myeloid leukemia

The efficacy and toxicity of carboplatin plus mitoxantrone in blast crisis of chronic myeloid leukemia (CMLBC) were evaluated. Between 1990 and 1996, 20 patients (11 males and nine females, median age of 49 years [range 30-75 years]) were treated with carboplatin, 250 mg/m(2)/day x 5 days as an infusion and mitoxantrone, 10 mg/m(2)/day x 3 days, IV bolus. Median time from diagnosis of CML to BC was 4.25 years (range 0-11 years). CMLBC was myeloid in 13 patients, lymphoid in six, and megakaryocytic in one. All patients were Philadelphia (Ph) chromosome positive; four had a single Ph chromosome, five had double Ph chromosome, three had abnormalities of chromosome 17, and eight had complex cytogenetic abnormalities. Prior treatment for chronic phase included hydroxyurea (12 patients), interferon-alpha (11 patients), cytarabine or all-trans retinoic acid, three patients each and other agents (four patients). Eight patients (five myeloid and three lymphoid) had an objective response (median duration, 3 months). Five had complete responses (CR) of 2, 3, 3, 6, and 6+ months duration, and three had partial responses (PR) for 1, 2, and 4 months. Seven patients died too early to evaluate (TETE): three died pancytopenic in <30 days from initiation of chemotherapy, two patients had pancytopenia for >30 days but had only blasts in their day 30 bone marrow, and two patients were pancytopenic >30 days but demonstrated trilineage marrow regeneration. Three of eight responders survived > or =1 year. Toxicity was primarily hematologic. The objective response rate was 61% (8/13) among those who did not die TETE and 40% among all treated patients. Carboplatin plus mitoxantrone are highly active in CMLBC, with marrow aplasia as the dose-limiting toxicity, and these agents deserve further study in CMLBC, perhaps in combination with tyrosine kinase inhibitors.