Carboplatin-containing Chemotherapy Research Articles

Olanzapine Plus Triple Antiemetic Therapy for the Prevention of Carboplatin-Induced Nausea and Vomiting: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial.

We evaluated the efficacy and safety of antiemetic therapy with olanzapine, a neurokinin-1 receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone for preventing chemotherapy-induced nausea and vomiting in patients receiving carboplatin-containing chemotherapy. Chemotherapy-naïve patients scheduled to receive carboplatin (AUC ≥5) were randomly assigned to receive either olanzapine 5 mg once daily (olanzapine group) or placebo (placebo group) in combination with aprepitant, a 5-HT3 RA, and dexamethasone. The primary end point was the complete response (CR; no vomiting and no rescue therapy) rate in the overall phase (0-120 hours). Secondary end points included the proportion of patients free of nausea and safety. In total, 355 patients (78.6% male, median age 72 years, 100% thoracic cancer), including 175 and 180 patients in the olanzapine and placebo groups, respectively, were evaluated. The overall CR rate was 86.9% in the olanzapine group versus 80.6% in the placebo group. The intergroup difference in the overall CR rate was 6.3% (95% CI, -1.3 to 13.9). The proportions of patients free of chemotherapy-induced nausea in the overall (88.6% in the olanzapine group v 75.0% in the placebo group) and delayed (89.7% v 75.6%, respectively) phases were significantly higher in the olanzapine group than in the placebo group (both P < .001). Somnolence was observed in 43 (24.6%) and 41 (22.9%) patients in the olanzapine and placebo groups, respectively, and no events were grade ≥3 in severity. The addition of olanzapine was not associated with a significant increase in the overall CR rate. Regarding the prevention of nausea, adding olanzapine provided better control in patients receiving carboplatin-containing chemotherapy, which needs further exploration.

Dietary Magnesium Replacement for Prevention of Hypomagnesemia in Patients With Ovarian Cancer Receiving Carboplatin-Based Chemotherapy.

Hypomagnesemia is a common side effect of platinum-based chemotherapy and predicts poor overall survival in some cancers. Standard magnesium replacement strategies are often inadequate for maintaining magnesium levels. We hypothesized that a daily dietary magnesium replacement approach through magnesium-rich foods would help maintain adequate magnesium levels during platinum-based treatment. We conducted a prospective feasibility study of magnesium-rich diets in patients 18 years and older with previously untreated ovarian cancer scheduled to receive carboplatin-containing chemotherapy of at least six consecutive cycles. Education about magnesium-rich diets was provided at enrollment and then weekly during chemotherapy. Feasibility was defined as ≥60% completion of dietary recalls and ≥280 mg average daily dietary magnesium intake across all patients. Twenty-one of 26 patients enrolled completed at least five chemotherapy cycles and were included in the analysis. Adherence to the study diet was 76%. Daily dietary magnesium intake was 100.5 mg at baseline and increased throughout each cycle: 6% of patients at baseline, 24% after the first cycle, and 67% after the fifth cycle reached ≥280-mg/day magnesium intake. Seven (33%) of 21 had at least one incident of hypomagnesemia. Patients who were adherent had significantly lower incidence of hypomagnesemia (19% v 80%, P = .03) and less need for intravenous magnesium (6% v 60%, P = .03) than those who were nonadherent. The study achieved primary feasibility objectives of retention and adherence to the study intervention. Weekly education about magnesium-rich diets was effective in increasing dietary magnesium intake. Adequate dietary magnesium appeared to be protective against hypomagnesemia.

EFFECTIVENESS AND SAFETY OF CARBOPLATIN-CONTAINING ANTITUMOR THERAPY REGIMENS IN A MODEL OF COEXISTANCE OF LUNG CARCINOMA AND TUBERCULOSIS

Introduction. Treatment of the coexistent pathology of lung cancer and tuberculosis remains the prerogative of experimental research, since the optimal treatment strategy for the coexistence of these two diseases has not yet been developed. The purpose was to study the effectiveness and safety of carboplatin-containing antitumor therapy regimens in combination with anti-tuberculosis chemotherapy. Material and methods. The study was conducted on 64 C57BL/6 mice aged two months with a previously modeled coexistant pathology of lung carcinoma and tuberculosis. Depending on the therapy, 4 groups were formed: 1 – control without treatment (n=16), 2 – antitumor (carboplatin + paclitaxel) + antituberculosis therapy (n=16), 3 – antitumor (carboplatin + pemetrexed) + antituberculosis therapy (n=16), 4 – antitumor (carboplatin + gemcitabine) + anti-tuberculosis therapy (n=16). The anti-tuberculosis therapy regimen included the administration of isoniazid, rifampicin, pyrazinamide and ethambutol. The antitumor effect (tumor growth index, tumor growth inhibition), antituberculosis effect (CFU per lung weight), toxicity (clinical blood test parameters, biometric indicators of internal organs), and survival were assessed. Statistical processing was carried out using non-parmetric statistics methods. Results. The lowest average body weight was recorded in group 4 from 7 to 21 days. The greatest differences between groups in the volume of the tumor node were observed from 12 to 16 days of the experiment under the influence of antitumor drugs. At the same time, the greatest inhibition of tumor growth was observed in group 4. On day 9 in group 2 there were signs of the myelo-immunosuppressive effect of antitumor therapy in the form of a decrease in the concentration of leukocytes, lymphocytes and monocytes. In the study groups, there were no statistically significant differences in the survival rate of the experimental and control groups. In all experimental groups, significantly lower spleen MC values were recorded, and in group 4, significantly lower liver MC values were also recorded. The highest level of mycobacterial load was recorded in the control group. The lowest CFU per lung weight was found in the carboplatin and gemcitabine treatment group. Conclusion. Carboplatin-containing chemotherapy regimens for lung carcinoma in tuberculosis-infected mice have both antitumor and antituberculosis effects. The most pronounced antimycobacterial activity was recorded when using a combination of antituberculosis therapy with carboplatin and gemcitabine.

Clinical and Economic Outcomes in Patients With Metastatic Urothelial Carcinoma Receiving First-Line Systemic Treatment (the IMPACT UC I Study).

The IMPACT UC I study assessed real-world treatment patterns, outcomes, healthcare resource utilization (HCRU), and costs in patients with metastatic urothelial carcinoma (mUC) receiving first-line (1L) systemic treatment after the FDA approval of 1L immune checkpoint inhibitor (ICI) monotherapy. This retrospective study used 100% Medicare fee-for-service claims from 1/1/2015 to 6/30/2019 to identify patients aged ≥18 years diagnosed with UC with evidence of metastatic disease, continuously enrolled for 6 months before and after initial diagnosis. Patients were grouped by 1L treatment: cisplatin-containing chemotherapy, carboplatin-containing chemotherapy, ICI monotherapy, or nonplatinum-containing therapy. Unadjusted time on 1L treatment (TOT), overall survival (OS), HCRU, and total healthcare costs were analyzed. Of 18 888 patients with mUC, 8630 (45.7%) had received identified 1L systemic treatment; platinum-containing chemotherapy was the most common (cisplatin-containing chemotherapy, 37.6%; carboplatin-containing chemotherapy, 30.2%). Cisplatin- and carboplatin-containing chemotherapy had the shortest time-to-treatment initiation (median, 1.7-3.0 months) and longest TOT (median, 4.0-4.3 months). Median OS was longest with cisplatin-containing chemotherapy (20.0 months) and shortest with ICI monotherapy (7.6 months). Cisplatin- and carboplatin-containing chemotherapy were associated with highest HCRU; total healthcare costs were approximately 2-fold higher with ICI monotherapy vs other 1L treatments ($10 359 vs $5042-$5709 per patient per month). 1L platinum-containing chemotherapy resulted in the longest median OS and highest HCRU, whereas 1L ICI treatment had the shortest median OS and the highest costs. Over 50% of patients diagnosed with advanced UC (aUC) received no systemic therapy, highlighting the importance of optimal 1L treatment decisions in aUC.

Olanzapine-containing antiemetic therapy for the prevention of carboplatin-induced nausea and vomiting

There remains an unmet clinical need for the control of chemotherapy-induced nausea and vomiting (CINV), particularly in the prevention of nausea and the delayed phase control. We evaluated the efficacy and safety of antiemetic therapy with olanzapine, a neurokinin-1 receptor antagonist, a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist and dexamethasone in patients receiving carboplatin-containing chemotherapy. Olanzapine inhibits signalling via multiple neurotransmitter receptors involved in CINV. Chemotherapy-naïve patients with lung cancer who received carboplatin-containing chemotherapy were enrolled in this phase-II study. Patients received olanzapine, aprepitant, a 5-HT3 receptor antagonist and dexamethasone. The primary endpoint was the complete response rate (no vomiting and no rescue therapy) during 120h after administration of chemotherapy agents. Thirty-three patients received olanzapine-containing antiemetic therapy. The overall complete response rate was 93.3% (95% confidence interval, 80.4-98.3%). The frequency of nausea was 15.2% in the delayed phase and 18.2% in the overall phase. Somnolence was observed in 16 patients. Adding olanzapine to antiemetic therapy with aprepitant, a 5-HT3 receptor antagonist and dexamethasone improved CINV control in patients receiving carboplatin-containing chemotherapy.

Hypomagnesemia and Survival in Patients with Ovarian Cancer Who Received Chemotherapy with Carboplatin.

Hypomagnesemia is a known side effect of several antineoplastic agents, but its impact on outcomes of patients with cancer is not well understood. We examined whether magnesium abnormalities affect survival in patients with ovarian cancer who receive chemotherapy containing carboplatin. We included patients with advanced ovarian cancer who had undergone surgery and chemotherapy between January 1, 2004, and December 31, 2014, at our institution. Inclusion criteria were age 18 years or older, pathology of high-grade serous carcinoma, first treatment (surgery or chemotherapy) within 60 days of diagnosis, and chemotherapy containing carboplatin. The final cohort consisted of 229 patients. Vital signs and laboratory tests were recorded at baseline and during the treatment course. The associations between magnesium abnormalities (and other clinical characteristics) and survival were analyzed. The median patient age was 64 years. Higher baseline heart rate (beats per minute; hazard ratio [HR] = 1.02, p = .002) and greater frequency of hypomagnesemia during the treatment course (HR = 1.05, p = .002) were significantly associated with shorter survival independent of completeness of tumor reduction (HR = 1.60, p = .02), and International Federation of Gynecology and Obstetrics stage (HR = 1.63, p = .01). Baseline heart rate and the frequency of hypomagnesemia episodes during treatment are prognostic of survival for patients with advanced ovarian cancer receiving carboplatin-containing chemotherapy and tumor reductive surgery. Future research is needed for strategies to detect and prevent hypomagnesemia in this patient population. Despite standard laboratory tests and intravenous magnesium replacement prior to each cycle of chemotherapy, hypomagnesemia remains a common side effect of platinum-based chemotherapy. This study revealed that frequent occurrence of hypomagnesemia during the course of treatment including carboplatin-containing chemotherapy and tumor reductive surgery was strongly predictive of shorter survival in patients with advanced ovarian cancer. Strategies to effectively mitigate hypomagnesemia, such as more frequent detection, dietary recommendations, and timely replacement, should be considered in the overall cancer treatment plan for these patients.

Prophylactic aprepitant is better than salvage for carboplatin-based chemotherapy: a propensity score-matched analysis.

Aprepitant prevents chemotherapy-induced nausea and vomiting (CINV) in carboplatin-containing chemotherapy. However, it is unknown whether aprepitant salvage therapy after the development of emesis is as effective as adding prophylactic aprepitant to doublet therapy with dexamethasone and a 5-HT3 receptor antagonist from the first cycle of chemotherapy. To compare the antiemetic efficacy of aprepitant between salvage and prophylactic administration in the second cycle of carboplatin-containing chemotherapy, twenty-two NSCLC patients who developed CINV in the first cycle of carboplatin-containing therapy without aprepitant (salvage group) and 44 patients who received aprepitant (prophylaxis group) were extracted from the pooled data of two clinical trials, with adjustment for age, sex, and chemotherapeutic regimen as co-variables using propensity score matching. In the second cycle of chemotherapy, both groups received aprepitant, and the rate of antiemetic complete response (no vomiting and no rescue therapy) at 5days after chemotherapy was compared. The prophylaxis group demonstrated a significantly better overall complete response rate (88.6%; 95% confidence interval [CI] 75.4-96.2) compared with that of observed for the salvage group (68.2%; 95% CI 45.1-86.1, p = 0.042). The prophylaxis group also demonstrated a significantly lower proportion of any-grade nausea (43.2%) and appetite loss (43.2%) than the salvage group (72.7%, p = 0.036 and 77.3%, p = 0.010, respectively). Adding aprepitant to doublet therapy from the first cycle of carboplatin-containing chemotherapy may be more effective than salvage use of aprepitant after the development of CINV.

Novel ex vivo ovarian cancer tissue explant assay for prediction of chemosensitivity and response to novel therapeutics

The majority of ovarian cancer patients present with advanced disease and despite aggressive treatment, prognosis remains poor. Response to first-line carboplatin-containing chemotherapy is usually good, however, recurrence rates and subsequent chemoresistance are very high and ultimately responsible for the fatal outcome of the disease. To improve treatment outcomes pre-clinical models that can predict individual patient response to 1st line chemotherapy and novel therapeutics are urgently required. In this study, we employed an ex vivo ovarian cancer tissue explant assay to assess response to carboplatin and an inhibitor of the extracellular matrix molecule, hyaluronan (4-methylubelliferone, 4-MU), shown to inhibit cancer metastasis. Cryopreserved ovarian cancer tissues were cultured on gelatine sponges for 48–120 h with increasing concentrations of carboplatin (0–400 μM) or 4-MU (1 mM) alone or the combination of both drugs. Effects on apoptosis and proliferation were assessed by immunohistochemistry using antibodies to cleaved caspase 3 or Ki67, respectively. The ex vivo tissue explant assay maintained viable tumor cells in an intact tumor microenvironment similar to the in vivo situation over the 120 h culture period. Carboplatin treatment promoted apoptosis in chemosensitive (P = 0.0047) but not chemoresistant cancer tissues. The combination of 4-MU (1 mM) and carboplatin (100 μM) significantly increased apoptosis (P = 0.0111) and reduced proliferation (P = 0.0064) in chemoresistant tissues. Overall, our results show that the ex vivo explant assay is a robust and cost effective model to assess chemosensitivity and the effect of novel therapeutics in ovarian cancer.

Antiemetic therapy for non-anthracycline and cyclophosphamide moderately emetogenic chemotherapy.

Although antiemetic management in cancer therapy has improved, chemotherapy-induced nausea and vomiting remain common and troubling adverse events. Chemotherapeutic agents are classified based on their emetogenic effects, and appropriate antiemetics are recommended according to this categorization. Chemotherapy categorized as moderately emetogenic is associated with a wide spectrum of emetic risks. Combined anthracycline and cyclophosphamide regimens have been recently reclassified as highly emetogenic chemotherapy regimen. This review focuses on antiemetic pharmacotherapy in patients receiving non-anthracycline and cyclophosphamide-based moderately emetogenic chemotherapy regimens. Combination therapy with a 5-hydroxytryptamine-3 receptor agonist, preferably palonosetron, and dexamethasone is the standard therapy in moderately emetogenic chemotherapy, although triple therapy with add-on neurokinin-1 receptor antagonist is used as an alternative treatment strategy. Among moderately emetogenic chemotherapy regimens, carboplatin-containing chemotherapy has considerable emetic potential, particularly during the delayed phase. However, the additional of a neurokinin-1 receptor antagonist to the standard antiemetic therapy prevents carboplatin-induced nausea and vomiting. For regimens including oxaliplatin, the benefit of adding neurokinin-1 receptor antagonist requires further clarification.

Predictive factors of pathological complete response in primary human epidermal growth factor receptor 2-positive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy

To investigate the predictive factors of pathological complete response (pCR) in primary human epidermal growth factor receptor 2 (HER2)-positive breast cancer treated with trastuzumab-based neoadjuvant chemotherapy (NAC). Totally 101 patients of primary HER2-positive breast cancer treated with trastuzumab-based NAC and subsequent curative surgical therapy in the Breast Disease Center of Peking University First Hospital from September 2007 to December 2014 were retrospectively reviewed. All patients were female with a median age of 53 (range 23 to 70) years.All patients received a taxanes- and carboplatin-containing chemotherapy, and trastuzumab was administered concurrently.A pCR, defined as the absence of invasive tumor cells in the breast and axillary lymph nodes, was achieved in 37.6% of patients (38/101). For analysis of the associations between clinicopathological factors and pCR, the χ(2) test or Fisher's exact test was used for univariate analysis, and multivariate Logistic regression analysis was performed to estimate OR and 95% CI. Tumor-infiltrating lymphocytes (χ(2)=14.981, P=0.000), hormone receptor (HR) status (χ(2)=9.513, P=0.002), and tumor grade (χ(2)=4.005, P=0.045) were significantly associated with pCR in univariate analysis. Tumor-infiltrating lymphocytes positive (OR=4.74, 95% CI: 1.87 to 12.01, P=0.001) and HR-negative (OR=3.28, 95% CI: 1.31 to 8.20, P=0.011) were independent predictive factors of pCR in multivariate analysis. Tumor-infiltrating lymphocytes-positive and HR-negative were independent predictive factors of pCR in primary HER2-positive breast cancer treated with trastuzumab-based NAC.

893P - Predictors of Hypersensitivity Reactions (Hsrs) in Patients Receiving Carboplatin-Based Chemotherapy for Ovarian Cancer

ABSTRACT Aim: Carboplatin offers high response rates and improved overall survival for women with ovarian cancer, but treatment may be limited by carboplatin-induced HSRs. We identified patients at high risk of carboplatin-induced HSRs that could be targeted for future prevention therapies. Methods: A retrospective chart review of 452 patients with ovarian cancer receiving a sixth or subsequent cycle of carboplatin-containing chemotherapy from 2006 to 2012 at Princess Margaret Cancer Centre (PMCC) in Toronto, ON was performed. Age, cumulative number of treatment cycles, cumulative carboplatin dose, co-administered chemotherapy, BRCA status, use of prophylactic diphenhydramine and other allergies were noted. The pattern of carboplatin administration was recorded as either continuous, short (≤12 months) or long interval (>12months) since last receiving carboplatin-containing chemotherapy. Predictors of HSRs were assessed using the Chi-square, student's T-test and a multivariable logistic regression model. Results: Carboplatin-induced HSRs occurred in 9% (n = 41/452) of patients, of which 4 were anaphylactic. Their median age was 57 (range 25 to 89). Sixteen percent received carboplatin alone; the remaining patients received co-administered Paclitaxel (74.5%), Caelyx (4.2%), Gemcitabine (2.4%) or another agent (2.7%). Thirty five percent received diphenhydramine prophylaxis. Univariable predictors of carboplatin-induced HSRs included the number of carboplatin cycles, other drug allergies and the platinum-free interval. Cumulative carboplatin dose, co-administered chemotherapy, diphenhydramine prophylaxis and BRCA status were not significant. In a multivariable model, factors predictive of HSRs included the administration of 8 to 10 cycles of carboplatin [OR 7.5 (95%CI 2.8-20.1), p Conclusions: Ovarian cancer patients receiving 8 to 10 cycles of carboplatin-containing chemotherapy and those with a long interval (>12 months) since last receiving carboplatin are at an increased risk of carboplatin-induced HSRs. These patients may be targeted for future prevention therapies. Disclosure: All authors have declared no conflicts of interest.

Abstract P3-14-07: Carboplatin plus paclitaxel compared with epirubicin plus paclitaxel as neoadjuvant chemotherapy for triple-negative breast cancer - A phase II clinical trial

Abstract Background Combination anthrathyclin-taxane regimens are the most widely-used neoadjuvant chemotherapy for triple negative breast cancer (TNBC), with objective response rates (ORR) of approximately 80% but poor pathologic complete response rates (pCR, 10%-25%) and survival. More effective chemotherapy regimens are needed. Several small clinical trials have suggested cisplatin- or carboplatin-containing chemotherapy can achieve higher pCR rates. However, no studies have compared the efficacy of platinum combination chemotherapy with a traditional anthrathyclin-taxane regimen. The objective of this study is to compare carboplatin plus paclitaxel with epirubicin plus paclitaxel in the neoadjuvant setting to determine the better choice for TNBC. Methods This is a single centre, open label, two-arm phase II clinical trial (NCT01276769). Patients with ER/PR/Her-2 negative breast cancer by immunohistochemistry from core needle biopsy were enrolled. All had indication for neoadjuvant chemotherapy. Patients were stratified according to clinical stage (II/III), and then randomized to receive paclitaxel (175 mg/m2, d1) and carboplatin (AUC = 5, d2), every 3 weeks for 4-6 cycles (PC arm) or epirubicin (75mg/m2, d1) plus paclitaxel (175 mg/m2, d2), every 3 weeks for 4-6 cycles (EP arm). The primary endpoint was pCR, which was defined as no residual invasive cancer in both the excised breast and axillary lymph node, or only carcinoma in situ. The secondary endpoints included ORR, safety, RFS (relapse-free survival) and OS (overall survival). Results A total of 91 patients were recruited (PC 47 patients, EP 44 patients) from April 2006 to December 2012. Median age was 47 years (range 24-73); 65% patients were premenopausal; 66% were at stage III; CK5/6 and EGFR positive rates were 63.01% (46/73), and 79.73% (59/74), respectively. 77.03% (57/74) had Ki-67 scores ≥ 20%. The proportion of patients with basal-like subtype (defined as CK5/6 or EGFR positive) in the two arms was 97.30% vs. 91.67 (p = 0.358). Eighty-five percent of patients completed 4-6 cycles of chemotherapy. ORR in the PC and EP arm was similar (89.4% vs. 79.6%, P = 0.195), but the pCR rate in the PC arm was significantly higher compared to the EP arm (38.6% vs. 14.0%, p = 0.016). The main G3/4 adverse event in both arms was neutropenia (72.3% vs. 63.6%, p = 0.500). Median follow-up period was 37 months (range 3-78 months), and 8 and 17 RFS events occurred in the PC and EP arms, respectively. Eighty-eight percent (22/25) of death events occurred in the first 3 years after diagnosis. Four-year RFS in the PC and EP arms were 71.1% vs. 52.8%, respectively (p = 0.080), and 4-year OS were similar (70.1% vs. 72.5% respectively, p = 0.980). For the whole group, pCR patients had significantly better 4-year RFS (90.9% vs. 50.1%, p = 0.001) and 4-year OS (100% vs. 64.9%, p = 0.002) compared with non-pCR patients. Conclusion Compared with the most widely-used EP chemotherapy, the PC regimen could significantly improve pCR rate for TNBC, and the 4- year RFS showed a trend towards improvement. Overall, pCR patients’ prognosis was much better than non-pCR patients. PC chemotherapy could be the preferred choice for TNBC neoadjuvant treatment. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-07.

Paraneoplastic Focal Segmental Glomerulosclerosis in a Patient with Lung Adenocarcinoma

Focal segmental glomerulosclerosis (FSGS) is extremely rare among paraneoplastic nephrotic syndromes. We herein report a case of lung adenocarcinoma with nephrotic syndrome caused by paraneoplastic FSGS. A 68-year-old man visited our hospital for an evaluation of a right hilar mass on chest radiography and supraclavicular lymphadenopathy. Because an aspiration biopsy of the supraclavicular lymph node revealed adenocarcinoma, the patient was diagnosed with lung adenocarcinoma. He also had nephrotic syndrome, and the pathological findings of the renal biopsy demonstrated FSGS. Standard-dose carboplatin-containing chemotherapy led to a partial response for lung cancer and improved the patient's nephrotic syndrome without causing any adverse renal effects.

Syndrome of inappropriate anti‐diuretic hormone secretion secondary to carboplatin after docetaxel‐carboplatin‐trastuzumab combination for early stage HER‐2 positive breast cancer

Carboplatin is a platinum analogue, widely used in the treatment of numerous cancer types including lung, genitourinary and ovarian cancers. It is also used in the adjuvant treatment of human epidermal growth factor receptor 2 positive breast cancer, where a non-anthracycline regimen is preferred. It is considered generally to be less toxic though potentially less efficacious than cisplatin, another platinum compound. Cisplatin is well recognized as causing hyponatremia, through the mechanism of renal salt wasting. Conversely, carboplatin has only rarely been associated with hyponatremia. We report here a case of severe hyponatremia occurring 6 days after adjuvant treatment with a carboplatin-containing chemotherapy regimen for early stage breast cancer. The mechanism of hyponatremia was consistent with the syndrome of inappropriate anti-diuretic hormone secretion based on biochemical and clinical findings, and response to fluid restriction. With no previously reported cases of docetaxel-associated or trastuzumab-associated hyponatremia, the causative agent was considered to be carboplatin. Additionally there was no recurrence of hyponatremia on recommencement of docetaxel and trastuzumab therapy. Hyponatremia secondary to carboplatin has been rarely reported in the literature, with only three previously reported cases. Although it is rare, oncologists should be aware of the potential for carboplatin to cause hyponatremia and the need to monitor electrolytes throughout therapy.

A prospective study on the incidence of delayed nausea and vomiting following administration of carboplatin-containing regimens for treatment of cancer without prophylactic aprepitant.

e19552 Background: Delayed nausea and vomiting following administration of carboplatin-containing chemotherapy regimen remains a clinically significant problem for patients with cancer despite administration of standard antiemetic prophylaxis (a 5-HT3 antagonist and dexamethasone). Methods: We report results of a prospective study to evaluate the incidence of delayed chemotherapy-induced nausea and vomiting (CINV) after the first cycle of treatment. Previously untreated patients with newly diagnosed cancer scheduled to receive carboplatin containing regimen (AUC 5 or above) (but no prophylactic aprepitant) were eligible to participate. Primary endpoint is the incidence of CINV after cycle 1 of chemotherapy. Secondary endpoints include the incidence of CINV after the third cycle and the gender differences in incidence of CINV. Patients completed the Functional Living Index Emesis (FLIE) questionnaires 24, 48, 72 and 96 hours after receiving chemotherapy. Telephone interviews were conducted 24-48 hours following chemotherapy to assess the severity and need for breakthrough medications for CINV. Results: The characteristics of 109 patients enrolled: 58% male, mean age 63.9 years (range 42-82 years) and 85% diagnosed with lung cancer. Twenty-two percent of patients reported moderate to severe CINV 72 hours after chemotherapy, with symptoms persisting as long as 96 hours in 23% of the patients after cycle 1. Multivariate analysis was performed to evaluate the association between gender and the incidence of CINV. There was no statistically significant difference in gender (p = 0.43) or between cycle 1 and cycle 3 (p = 0.19). Conclusions: Without prophylactic aprepitant administration, one-fifth of cancer patients receiving carboplatin containing regimen had moderate to severe delayed CINV. Percentage of patients with delayed CINV 24 hrs 48 hrs 72 hrs 96 hrs Cycle 1 9.71% 13.73% 21.78% 22.77% Cycle 3 4.00% 12.77% 14.58% 16.00% No significant financial relationships to disclose.

Results of an Open-Label Study to Evaluate the Efficacy and Tolerability of Aprepitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting Associated with Carboplatin-Containing Chemotherapy in Patients with Ovarian Cancer, Primary Peritoneal, or Fallopian Tube Carcinoma (Stage I-IV) or Papillary Serous Cancer of the Uterus

PurposeAprepitant might offer an advantage in preventing acute/delayed chemotherapy-induced nausea and vomiting (CINV). This study integrated palonosetron and dexamethasone into the regimen to determine the efficacy and safety of this combination. Patients and MethodsFifty patients were enrolled; 49 were evaluable. Main inclusion criteria were (1) diagnosis of ovarian (OV), primary peritoneal (PP), or fallopian tube (FT) carcinoma (stage I-IV) or papillary serous cancer of the uterus (UPSC); (2) patients naive to emetogenic chemotherapy Hesketh ≥ level 4; (3) scheduled to receive paclitaxel 175 mg/m2 intravenously (I.V.) and carboplatin AUC 6 I.V.; able to read/understand the Functional Living Index–Emesis questionnaire. ResultsMedian age was 61 years, 60% had Eastern Cooperative Oncology Group performance status of 0, 86% had previous surgery (74% OV, 12% PP, 8% UPSC, and 6% FT). The metastases rate was 30%; 21% were visceral metastasis. Eighty-six percent of patients reported no vomiting or use of rescue medications during cycle 1 (95% and 100% in cycles 2–3 and 4–6, respectively) and were deemed as complete responders. Grade 3/4 treatment-related adverse events limited to neutropenia (6%). Grade 1/2 toxicities > 5% included nausea (12%), alopecia, constipation, arthralgia (8% each), and anemia (6%). Some toxicities might have been related to chemotherapy and were not related to the aprepitant, palonosetron, or dexamethasone. ConclusionThe addition of aprepitant to palonosetron and dexamethasone appears to be very well tolerated. This combination is effective in the prevention of chemotherapy-induced nausea and vomiting when used with emetogenic therapy (paclitaxel and carboplatin).

Preliminary results of an open-label study to evaluate the efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with carboplatin-containing chemotherapy regimen in patients with ovarian cancer

19652 Background: The use of aprepitant has been shown to offer an advantage in preventing acute and delayed chemotherapy- induced nausea and vomiting (CINV). This study integrates palonosetron and dexamethasone into the regimen to determine the efficacy and safety of this combination. Methods: 50 patients (pts) have enrolled; data has been submitted for 43. Main inclusion criteria were: diagnosis of ovarian (OV), primary peritoneal (PP), fallopian tube (FT) carcinoma Stage I-IV, or papillary serous cancer of the uterus (UPSC); naive to emetogenic chemotherapy Hesketh ≥Level 4, is scheduled to receive paclitaxel 175 mg/m2 IV and carboplatin AUC=6 IV; is able to read and understand the Functional Living Index - Emesis (FLIE) questionnaire. Results: Median age was 61 years, 60% ECOG=0, 86% prior surgery; 68% OV, 14% PP cancers, 7% UPSC, and 5% FT. Metastases were noted in 30% of pts, 21% had visceral metastasis. To date, 70% of patients (32/46) have reported no vomiting, or use of rescue medications during the study and are deemed as complete responders. Based on the 35 pts for whom complete patient diaries have been submitted thus far, the complete response rate is 91% (32/25), compared to 50% (aprepitant alone [The MEC Trial]). No Grade 3–4 treatment related adverse events were reported; Grade 1–2 toxicities included neutropenia (10.5%); anemia, constipation, and nausea (7.9%, each), and fatigue, dyspepsia, and arthralgia (5.3%, each). Some of the toxicities may be related to the chemotherapy, and are not treatment-related to the aprepitant, palonsetron, or dexamethasone. Conclusions: The addition of aprepitant to palonsetron and dexamethasone appears to be very well tolerated. This combination is effective in the prevention of chemotherapy-induced nausea and vomiting when used with emetogenic therapy such as paclitaxel and carboplatin. This research was supported, in part, from a research grant from Merck &amp; Co., Inc. Whitehouse Station, NJ. No significant financial relationships to disclose.

Carboplatin chemotherapy in a pregnant patient with undifferentiated ovarian carcinoma: case report and review of the literature

There are already 12 reports of women treated by chemotherapy for epithelial ovarian cancer during pregnancy. However, most cases received chemotherapy of single cisplatin or cisplatin-based regime, and only four cases received carboplatin-containing chemotherapy. We report the case of a woman treated with single-agent carboplatin during pregnancy. The patient underwent bilateral salpingo-oophorectomy at 18 weeks of gestation and was diagnosed as having stage IC undifferentiated ovarian carcinoma. She was treated with four courses of carboplatin (area under the curve = 6.0) chemotherapy during pregnancy without severe toxicity. At 33 weeks of gestation, cesarean section was performed, followed by total hysterectomy, omentectomy, and pelvic and para-aortic lymphadenectomy. No residual disease was histologically shown. The patient underwent additional chemotherapy with carboplatin and paclitaxel. After one year of follow-up, the baby shows normal growth and the patient has no evidence of disease. Postponing the termination of pregnancy by single-agent carboplatin chemotherapy during pregnancy might be considered as an option for therapy in selected women with ovarian malignancies.

A phase II trial of carboplatin for intraocular retinoblastoma

Retinoblastoma patients with RB1 germline mutations are at risk of developing second malignancies and external beam radiation therapy increases the risk. Carboplatin-containing chemotherapy regimens in conjunction with local therapies have been investigated for intraocular retinoblastoma, but the lack of data regarding the efficacy of single agent intravenous carboplatin prompted this phase II study. Twenty-five patients (43 eyes) were treated with intravenous carboplatin (18.7 mg/kg for patients < 12 kg, 560 mg/m(2) for patients >/= 12 kg). Patients received a median of two cycles of carboplatin (range one to five cycles) beginning at a median age of 5 months (range 14 days to 22 months). All patients were extraocular disease free during the follow-up period (median 76.3 months). Responses were noted in 33 of 36 evaluable eyes (92%). The 5-year overall ocular and ocular event-free survivals were 93.3% (95% CI, 84.4-100%) and 43.5% (95% CI, 25.8-61.3%) for eyes treated for Reese-Ellsworth (RE) group 1-3 disease and 25.0% (95% CI, 1.0-50.0%) and 8.3% (95% CI, 0-24.0%) for RE group 4-5 disease, respectively. No non-hematopoietic serious or permanent toxicities related to the chemotherapy were observed. When used as a neoadjuvant agent, carboplatin usually leads to objective responses of intraocular retinoblastoma. The 5-year ocular event-free survival appears inferior to other protocols using more extensive chemotherapy, but with greater radiation therapy usage, overall ocular survival rate for RE group 1-3 eyes was excellent.

A phase II study of a paclitaxel and oxaliplatin combination in platinum-sensitive recurrent advanced ovarian cancer patients

PurposeA multicentric, phase II study to evaluate the efficacy and safety of the combination paclitaxel and oxaliplatin in patients with platinum-sensitive recurrent ovarian cancer. Patients and methodsPatients received 175 mg/m2 paclitaxel (over 3 h) followed by 130 mg/m2 oxaliplatin (over 2 h) every 21 days for up to nine cycles without hydration or primary granulocyte colony-stimulating factor prophylaxis. Patients had to have an Eastern Cooperative Oncology Group performance status of 0–2 and to have received no more than one prior cisplatin- and/or carboplatin-containing chemotherapy regimen with a platinum-progression-free interval ≥6 months. ResultsOf the 105 patients enrolled and treated, 98 were eligible. An overall response rate of 81% (79 of 98 patients) (95% confidence interval 71% to 88%) was observed according to RECIST criteria (third party reviewed), and 88% (86 of 98) when this was complemented with CA-125 response. With a median follow up of 43.6 months (range 30.2–64.2) the median progression-free survival was 10.2 months (range 0.3–21.4) and the overall survival 32.4 months. Seven hundred and eight cycles were administered (median seven per patient; range one to nine). A total of 67% of patients experienced National Cancer Institute Common Toxicity Criteria grade 3–4 neutropenia, including 8% with concomitant febrile episode, without treatment-related deaths. Ninety-three per cent of patients experienced neuropathy of grade 1 or more, including 25% with cumulative reversible peripheral neuropathy of grade 3–4. Oxaliplatin doses were reduced in 30 patients due to neurotoxicity. ConclusionsThe oxaliplatin/paclitaxel combination can be administered in an outpatient setting every 3 weeks without specific measures. The high level of activity and its duration observed warrants further evaluation of this combination in pretreated platinum-sensitive advanced ovarian cancer patients.