Carboplatin-containing Regimens Research Articles

Abstract P4-07-60: Identification of Optimal Carboplatin Containing Regimen for Triple Negative Breast Cancer

Abstract Background: Current management for triple negative breast cancer (TNBC) involves chemotherapy and immunotherapy systemic treatments. TNBC treatment remains a challenge, with up to 40% of those treated using standard methods for stage I to III TNBC experiencing recurrence. Currently, the optimal carboplatin regimen for TNBC is yet to be defined. In our previous study, we identified an optimal carboplatin containing chemotherapy regimen that improved patient outcomes. In this study, we expanded the cohort as an extension of the previous prospective study to further verify these promising results. Patients and Methods: We performed a retrospective review of 37 TNBC patients who had < 10% estrogen and progesterone receptor positivity and were human epidermal growth factor receptor-2 (HER2) negative. This study was originally done in an adjuvant setting, but patients with locally advanced tumors received neoadjuvant chemotherapy. Patients received dose-dense Adriamycin, cyclophosphamide, and paclitaxel every two weeks for sixteen weeks. Adriamycin (60 mg/m^2) and cyclophosphamide (600 mg/m^2) were given intravenously every two weeks for four cycles, followed by paclitaxel (175 mg/m^2) every two weeks for four cycles. Carboplatin with an area under the curve of 6 was added to cycles two and four of paclitaxel. Last, we changed the parameters of continuing chemotherapy to allow platelet counts > 70,000 × 10^9. Only paclitaxel could be modified for neuropathy. Results: Of 37 patients enrolled in this trial, 35 patients survived without recurrence, one required a dose reduction in paclitaxel, and one has incomplete staging as grade is still pending. The two patients that did experience recurrence died. Of these two patients, the first had American Joint Committee on Cancer (AJCC) 7 stage IIIC cancer, and the second had two separate TNBCs at presentation – AJCC-7 IIB cancer of the right breast and AJCC-7 IIA cancer of the left breast. Under the AJCC-8 system, the first patient had AJCC-8 IIIB cancer, while the second patient had AJCC-8 IIIB cancer of the right and left breasts. These data suggest a completion rate of 97%, overall survival (OS) rates of 95% (AJCC-7 & 8), and progression free survival (PFS) rates of 95% and 94% (AJCC-7 & 8, respectively; Table 1). Additional stage-specific survival metrics and patient staging information are available in Table 1. Median follow-up in this study was 3.14 years. This is consistent with data from our previous study with significant PFS benefit over historic chemotherapy. All patients completed this regimen with no dose reductions of carboplatin and a 32% dose reduction in paclitaxel due to neuropathy. Toxicity was established in our previous study. The favourable toxicity profiling of the regimen allowed maximal tolerance for patients. Conclusion: Although administration of carboplatin with chemotherapy for TNBC is known to be beneficial, the ideal carboplatin containing regimen has not been identified because of concerns regarding toxicity and low completion rates. Here, an optimal carboplatin-containing regimen identified in our previous clinical trial led to 95% overall survival rates (AJCC-7 & 8), 95% and 94% progression free survival rates (AJCC-7 & 8, respectively), and a 97% completion rate for 37 TNBC patients. A limitation is that this is a small single center trial, and plans are underway to test this regimen with immunotherapy in a larger randomized control trial. Table 1: Patient Staging and Survival Metrics. Citation Format: Geoffrey J. Rempel, Claire S. Rim, Abdulkadir Hussein, Alina Bocicariu, Swati Kulkarni, Rasna Gupta, John Matthews, Amin Kay, Lisa Porter, Caroline Hamm. Identification of Optimal Carboplatin Containing Regimen for Triple Negative Breast Cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-60.

Adding aprepitant to palonosetron does not decrease carboplatin-induced nausea and vomiting in patients with gynecologic cancer

BackgroundRecently, aprepitant has been recommended in carboplatin-based regimens, but there are limited reports on the efficacy of administering aprepitant, palonosetron, and dexamethasone (DEX) in carboplatin-containing regimens. Moreover, because aprepitant is an expensive drug, confirming its effectiveness is very important from the medical cost perspective. In this study, we examined the efficacy of prophylactically administered aprepitant, palonosetron and DEX, in paclitaxel and carboplatin (TC) combination chemotherapy.MethodsPatients with gynecologic cancer who were treated with paclitaxel (175 mg/m2) and carboplatin (area under the curve, AUC = 5–6) combination chemotherapy were retrospectively evaluated. The complete response (CR) rate, severity of nausea, and incidence of anorexia in the first course were compared between patients who did not receive aprepitant (control group) and those who received (aprepitant group).ResultsThe 106 patients were divided into two groups, consisting of 52 and 54 the control and aprepitant groups, respectively, and the patient background showed no significant difference between both groups. The CR rate of the overall phase between the control and aprepitant groups was 73.1 vs. 74.1%, that in the acute phase was 98.1 vs. 100%, and in the delayed phase was 75.0 vs. 74.1%, respectively, without any significant difference. The severity of nausea and incidence of anorexia were also not significantly different between both groups.ConclusionsThe results of the study suggest that adding aprepitant to palonosetron and DEX does not prevent carboplatin-induced nausea and vomiting in gynecologic cancer patients. Therefore, adding aprepitant to palonosetron does not decrease carboplatin-induced nausea and vomiting in patients with gynecologic cancer.

Incidence of Hypersensitivity Reactions to Carboplatin or Paclitaxel in Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer With or Without BRCA1 or BRCA2 Mutations.

The association of BRCA mutation status with hypersensitivity reactions (HSRs) to carboplatin has gained interest in recent years, particularly in patients with ovarian, fallopian tube, and primary peritoneal cancer. The primary objective of this study is to determine whether the presence of BRCA mutations increased the likelihood of HSRs to carboplatin. The incidence of HSRs to paclitaxel and symptom grade based on the Common Terminology Criteria for Adverse Events, version 4.0, were explored as secondary endpoints. A retrospective chart review of patients with ovarian, fallopian tube, or primary peritoneal cancer at the University of Arizona Cancer Center who underwent treatment with carboplatin-containing regimens and received genetic testing was performed. Institutional review board approval was obtained for this study. Fisher’s exact test was used to analyze the primary outcome. Out of 167 initial patients, 62 with germline test results constituted the evaluable sample. 15 of 62 (24.2%) BRCA-tested patients were treated with carboplatin monotherapy, while 44 of 62 (71.0%) patients were treated with paclitaxel-containing regimens. Hypersensitivity reactions occurred in 4 of 13 (30.8%) BRCA-mutated patients and 22 of 49 (44.9%) BRCA wild-type patients (p = .5291). Hypersensitivity reactions to paclitaxel occurred in 1 of 13 (7.7%) BRCA-mutated patients and 26 of 49 (53.1%) BRCA wild-type patients (p = .0039). Overall, there were 11 grade 1 reactions, 14 grade 2 reactions, and 16 grade 3 reactions to carboplatin. All reactions to carboplatin in BRCA-mutated patients were grade 1. All paclitaxel reactions manifested as grade 2. The sample size was the main study limitation. The presence of BRCA mutations was not statistically significantly associated with a higher incidence of HSRs to carboplatin, but was statistically significant with regards to paclitaxel.

Pathological complete response rate (pCR) in thirty-three women with triple-negative breast cancer (TNBC) treated with a neoadjuvant carboplatin-based regimen.

e12099 Background: The purpose of this retrospective case series was to assess pCR rate, progression-free survival and prognostic factors in TNBC. Methods: We reviewed medical records for 33 consecutive female patients with TNBC (41% node+) treated between July 2015 and April 2018 with neoadjuvant paclitaxel 80 mg/m2 IV weekly plus concurrent carboplatin (AUC 4) every 3 weeks for a total of 12 weeks followed by dose-dense doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 every 2 weeks for a total of 4 cycles. Surgical pathology was studied to determine the presence or absence of residual disease at surgery. Age at treatment, tumor stage, subsequent hospitalizations, and genetic testing were recorded. Patients with residual disease were treated with adjuvant capecitabine 1500 mg PO BID, one week on, one week off, for 6 monthly cycles ± radiation; some patients with a complete pathological response also received postoperative radiation. Results: Among 33 patients, 17 patients had pCR (52%, median age 58 yrs), 10 had a partial response and 6 had no response or progression (median age 63.5). After surgery 24 patients received radiation therapy (XRT). There were 6 hospitalizations, 3 that were treatment related, 2 for neutropenic fever and one for renal failure induced by carboplatin; all 3 resulted in chemotherapy dose reductions; all 3 had pCR. 3 progressions/recurrences were recorded: 2 after treatment and 1 progression during treatment. Two deaths occurred, 1 secondary to progressive disease. Median progression free survival time was 8.5 months (range 0.1 to 24.0 mos). Median time since diagnosis is 16.7 months (range 8.1 to 37.6 mos). There was no significant difference in the median age of patients who had a pCR compared with patients with residual disease. Conclusions: We observed pCR in patients with TNBC treated with a pre-operative carboplatin-containing regimen (superior to historical pCR rates in patients receiving taxanes and anthracyclines only). Although there are insufficient data to demonstrate increased overall survival, we show an improvement in prognosis with a carboplatin-containing regimen for TNBC.

Abstract P1-13-08: A prospective non-randomized clinical trial of adjuvant carboplatin chemotherapy in triple negative breast cancer

Abstract Background: The addition of carboplatin in the neoadjuvant setting has demonstrated improved outcomes in patients with triple negative breast cancer (TNBC). Carboplatin in the adjuvant setting has not been demonstrated to be an accepted regimen to date. This trial addresses this issue. Methods: The primary objectives of this study were to assess the toxicity of an adjuvant carboplatin-containing regimen for early stage TNBC patients, and to correlate outcomes with molecular markers including Spy-1. Secondary objectives included determination of progression free (PFS) and overall survival (OS), and comparing these to our institutional historical controls. Patients received the backbone of a dose dense anthracycline, taxane, cyclophosphamide (DD ACT), with the addition of carboplatin. Results: Ninety patients with stage I to III patients with triple negative breast cancer were accrued to this trial between Jan 2011 and June 2017. We discovered that DD ACT with carboplatin with an AUC of 5 given on the second and last paclitaxel was well tolerated. Chemotherapy delays were minimized when the parameters for administration of the carboplatin was to allow chemotherapy to proceed if the platelet count was >/= 70,000 x10^9/L and dose adjustment of paclitaxel was allowed based on neuropathy. There were no grade 4 adverse events. 4% of patients had grade 3 peripheral neuropathy (PN), 28% had grade 2 PN and 45% had grade 1 PN. Results of molecular profiles will be reported. Univariate analysis are reported, and were found to be very promising. Using log-rank statistic, a trend to improvement in overall survival was found when compared to historical controls (p=0.089). Median follow-up is 24 months. Longer follow-up is necessary to determine PFS and overall survival benefit. Conclusion: If considering an adjuvant regimen for triple negative breast cancer patients DDAC/TC with the carboplatin administered with an AUC of 5 on the second and fourth taxol of DDACT is a well-tolerated regimen. Univariate Analysis Comparing Carboplatin vs Historical Controls that did not receive CarboplatinVariableHistorical (no carbo)Carbo containing chemop overall n = 179n = 82 Age56.3 (13.1)49.8 (11.0)< 0.001Stage0.188Stage I47 (26.3%)15 (18.3%) Stage II88 (49.2%)50 (61.0%) Stage III44 (24.6%)17 (20.7%) Grade0.011Grade 18 (4.5%)0 (0.0%) Grade 233 (18.4%)7 (8.8%) Grade 3138 (77.1%)73 (91.2%) Remission Status0.009In Remission126 (70.4%)70 (86.4%) Relapsed53 (29.6%)11 (13.6%) Survival< 0.001Alive121 (67.6%)73 (90.1%) Deceased58 (32.4%)8 (9.9%) Citation Format: Hamm C, Kulkarni S, Gupta R, Mathews J, Amin K, Hussein A, Porter L. A prospective non-randomized clinical trial of adjuvant carboplatin chemotherapy in triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-13-08.

Efficacy of triple antiemetic therapy (palonosetron, dexamethasone, aprepitant) for chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based, moderately emetogenic chemotherapy.

BackgroundChemotherapy-induced nausea and vomiting (CINV) is a major adverse toxicity of cancer chemotherapy. Recommended treatments for prevention of CINV vary among published guidelines, and optimal care for CINV caused by moderately emetogenic chemotherapy has not been established. This study assessed the efficacy and safety of triple antiemetic therapy comprising palonosetron, dexamethasone and aprepitant for carboplatin-based chemotherapy. Chemotherapy-naïve patients with lung cancer scheduled for a first course of a carboplatin-containing regimen formed the study cohort. Patients were pretreated with antiemetic therapy comprising palonosetron (0.75 mg, i.v.) and dexamethasone (9.9 mg, i.v.) on day 1, and aprepitant (125 mg, p.o.) on day 1 followed by 80 mg on days 2 and 3. Primary endpoint was the proportion of patients who did not experience vomiting and did not require rescue medication [complete response (CR)] in the acute phase (0–24 h), late phase (24–168 h) and overall. Secondary endpoint was the proportion of patients who experienced no vomiting episodes and no more than mild nausea without the need for rescue medication [complete control (CC)].ResultsPrevalence of a CR during the acute phase, delayed phase, and overall was 100, 91.9 and 91.9%, whereas that of CC was 100, 84.4 and 84.4%, respectively. The most common adverse event was mild constipation; severe adverse events related to antiemetic treatment were not observed.ConclusionTriple antiemetic therapy comprising palonosetron, dexamethasone and aprepitant shows excellent effects in the prevention of CINV in patients receiving a carboplatin-containing regimen.

Efficacy of triple antiemetic therapy (palonosetron, dexamethasone, aprepitant) for chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based, moderately emetogenic chemotherapy.

226 Background: Chemotherapy-induced nausea and vomiting (CINV) is a major adverse toxicity of cancer chemotherapy. Recommended treatments for prevention of CINV vary among guidelines, and optimal care for CINV caused by moderately emetogenic chemotherapy has not been established. This study assess efficacy and safety of triple antiemetic therapy consist palonosetron, dexamethasone and aprepitant for carboplatin-based chemotherapy. Methods: Chemotherapy-naïve patients with lung cancer scheduled for a first course of a carboplatin-containing regimen formed the study cohort. Patients were pretreated with antiemetic therapy consist palonosetron (0.75 mg, i.v.) and dexamethasone (9.9 mg, i.v.) on day 1, and aprepitant (125 mg, p.o.) on day 1 followed by 80 mg on days 2 and 3. Primary endpoint was the proportion of patients who did not experience vomiting and did not require rescue medication (complete response (CR)) in the acute phase (0-24 h), late phase (24-168 h) and overall. Secondary endpoint was the proportion of patients who experienced no vomiting episodes and no more than mild nausea without the need for rescue medication (complete control (CC)). Results: Prevalence of a CR during the acute phase, delayed phase, and overall was 100%, 91.9% and 91.9%, whereas that of CC was 100%, 84.4% and 84.4%, respectively. Most common adverse events were mild constipation; severe adverse events related to antiemetic treatment were not observed. Prevalence of a CR during the acute phase, delayed phase, and overall was 100%, 91.9% and 91.9%, whereas that of CC was 100%, 84.4% and 84.4%, respectively. Most common adverse events were mild constipation; severe adverse events related to antiemetic treatment were not observed. Conclusions: Triple antiemetic therapy comprising palonosetron, dexamethasone and aprepitant shows excellent effects in preventing CINV in patients receiving a carboplatin-containing regimen. Clinical trial information: UMIN000017877.

Hypersensitivity reactions to carboplatin in children with low-grade gliomas

The prognosis of pediatric low-grade gliomas is relatively favorable, but unresectable progressive tumors remain a challenge. Chemotherapy including carboplatin-containing regimens can delay the need for radiation therapy in young children. However, hypersensitivity reactions to carboplatin can at times be a severe complication. We have retrospectively evaluated and characterized the hypersensitivity reactions associated with carboplatin administration in pediatric low-grade glioma patients treated on an outpatient basis according to the SIOP/GPOH (International Society of Pediatric Oncology/ Gesellschaft fur Padiatrische Onkologie und Hamatologie) low-grade glioma 1996 protocol, and also reviewed the literature. Of nine patients consecutively treated with carboplatin, seven (78%) developed carboplatin hypersensitivity reactions. The first hypersensitivity reactions (always grade 2) occurred after a median of nine courses (range, 7-12). Although desensitization has been used successfully, there have been reports of severe cases of allergic reaction to carboplatin despite desensitization, including anaphylaxis and death. Since carboplatin hypersensitivity reactions are common and desensitization has not been proven to be safe, efforts should be made to design future therapy protocols for low-grade gliomas with clear guidelines on how to substitute carboplatin when hypersensitivity reactions occur. (J Pediatr Neurol 2004; 2(3): 151-155).

FINAL RESULTS OF A PROSPECTIVE MULTI-INSTITUTIONAL PHASE II STUDY OF EVEROLIMUS (RAD001), AN MTOR INHIBITOR, IN PEDIATRIC PATIENTS WITH RECURRENT OR PROGRESSIVE LOW-GRADE GLIOMA. A POETIC CONSORTIUM TRIAL

BACKGROUND: Purpose: The ras/raf signaling pathway is crucial in the development of pediatric low-grade gliomas (LGGs). Aberrant ras/raf signaling is involved in tumorigenesis through promotion of cell proliferation, survival, and differentiation in sporadic LGG. Everolimus (RAD001) is a potent and selective inhibitor of mTOR, a downstream element of the ras/raf pathway. The activity, safety and pharmacokinetics of everolimus in pediatric patients with radiographic recurrent/progressive LGG are presented. METHODS: Pediatric patients with radiographic progressive or recurrent LGGs without neurofibromatosis type I were treated with oral everolimus 5mg/m2/dose once daily. Therapy was provided for 28 days (one cycle) and could be repeated for a total of 12 cycles. Response, as determined by standard 2-D MRI criteria, was assessed for all patients. Pharmacokinetics, pharmacogenetics, pharmacodynamic parameters including inhibition of p70s6 kinase activity, 4E-BP1 phosphorylation inhibition and suppression of cMyc expression, as well as the toxicity profile of everolimus were evaluated. RESULTS: Twenty-three patients with a median age of 9 years (range, 3–17 years) were enrolled, all of whom had received prior chemotherapy (average # regimens = 2.7) including progression after a carboplatin-containing regimen. Median number of cycles of therapy was 10 (range, 1-12). Responses were determined by blinded central review and included 4 patients with PR (>50% decrease) and 13 with stable disease. Six patients had progressive disease by one year. Overall therapy was well tolerated; two patients discontinued therapy due to mouth sores (n = 1) and withdrawal of consent (n = 1). Everolimus PK parameters were similar to those previously reported in both adult and pediatric patients and drug trough levels were maintained above 5ng/ml. Pharmacodynamic analysis demonstrated inhibition of downstream targets of mTOR including phospho-S6 kinase, 4E-BP1 phosphorylation and cMyc expression within 14 days of initiation of everolimus therapy and this inhibition was maintained throughout the treatment period. CONCLUSIONS: Everolimus was well tolerated in pediatric patients with progressive or recurrent LGGs and demonstrated activity in this multiply recurrent/progressive patient population. Incorporation of everolimus into frontline LGG therapy is being proposed. SECONDARY CATEGORY: Clinical Neuro-Oncology.

Carboplatin-containing regimens as front-line treatment for advanced non-small-cell lung cancer in two groups of elderly

Objectives: We evaluated the impact of a carboplatin-based doublet in two groups of elderly patients with advanced non-small cell lung cancers (NSCLC).Materials and Methods: A retrospective analysis of all consecutive elderly patients (≧70 year old) with advanced NSCLC who received a carboplatin-based doublet as front-line therapy at our medical oncology unit was performed.Results: In the study, 57 consecutive elderly patients with advanced NSCLC were included. Carboplatin was combined with vinorelbine in 41 patients (71·9%) and with gemcitabine in 16 patients (28·1%). Overall, a total of 227 cycles were administered to 57 patients – 142 cycles were administered to patients in group 1 and 85 cycles were given to patients in group 2 – median number of administered cycles per patient was 4 (range 1–6). Of the patients, 35 (62%, group 1) were ‘young-old’ (70–74-year old) and 20 (38%, group 2) were ‘old-old’ (75–82-year old). Toxicity was mild in both subgroups (grade 3–4 neutropenia in 17·1% of group 1 and in 9·1% of group 2). At the univariate analysis, the median overall survival (OS) was 10·07 months (P = 0·789, 95% CI: 8·49–11·64), 10·1 months in group 1 and 9·8 months in group 2.Conclusions: This evaluation shows the safety and efficacy of a carboplatin-based doublet given as first-line chemotherapy in elderly advanced NSCLC patients. The combination with vinorelbine or gemcitabine is associated with a very good toxicity profile that does not seem to have a detrimental effect on efficacy.

Platinum-containing regimens as front-line treatment of advanced non-small cell lung cancer in two groups of elderly (≥ 70 year old) patients of different age.

e20617 Background: Elderly patients with advanced Non-Small Cell Lung Cancer (NSCLC) are underrepresented in clinical trials. Therefore we sought to evaluate the impact of a platinum-based doublet, given as a front-line chemotherapy, in two groups of elderly patients of different age with advanced NSCLC. Methods: A retrospective analysis of all consecutives elderly patients ( ≥70 year old) with advanced NSCLC who received a platinum based doublet as front line therapy at our Medical Oncology Unit from February 2005 to September 2011 was performed. The general case study was divided in two groups of patients of different age: “young-old” patients (70-74 year-old) and “old-old” patients (75-81 year-old). Results: Sixty-two consecutive elderly patients with advanced NSCLC were included in this study. Forty patients (65%) were “young-old” patients (group 1, median age 72 years) and 22 (35%) were “old-old” patients (group 2, median age 77 years). Overall, a total of 249 cycles were administered to the 62 patients; 164 cycles were administered to patients in group 1 and 85 cycles were given to patients in group 2; median number of administered cycles per patient was 4 (range 1-6) in both groups. Relevant clincal variables such as sex, stage, ECOG PS, Charlson score and histology were evenly distributed between the two subgroups. Regarding the type of first line chemotherapy, the great majority (92%) was treated with a carboplatin-containing regimen while only five patients (8%) received a cisplatin-based doublet: notably, all these patients are in group 1. Toxicity was mild, with grade 3-4 neutropenia in 17% of group 1 patients and in 9% of group 2 patients. Median OS was 9.8 months in both groups. Conclusions: This retrospective evaluation shows the safety and efficacy of a platinum-based doublet given as first-line chemotherapy in elderly advanced NSCLC patients. For several reasons, including the ease of administration, carboplatin is the preferred platinum analogue. The combination with vinorelbine or gemcitabine is associated with a very good toxicity profile that does not seem to have a detrimental effect on efficacy.

Mistletoe as complementary treatment in patients with advanced non-small-cell lung cancer treated with carboplatin-based combinations: A randomised phase II study

IntroductionMistletoe preparations, such as iscador, are common complementary medications. This randomised phase II study of iscador combined with carboplatin-containing regimens was conducted in chemotherapy-naïve advanced non-small-cell lung cancer (NSCLC) patients to assess its influence on chemotherapy-related side-effects and QoL. MethodsPatients with advanced NSCLC were randomised to receive chemotherapy alone or chemotherapy plus iscador thrice weekly until tumour progression. Chemotherapy consisted of 21-day cycles of carboplatin combined with gemcitabine or pemetrexed. ResultsSeventy-two patients (control: 39; iscador: 33) were enrolled in the study. Most (65%) were in stage IV, and 62% had squamous histology. Median overall survival in both groups was 11months. Median TTP was 4.8months for the controls and 6months in the iscador arm (p=NS). Differences in grade 3–4 haematological toxicity were not significant but more control patients had chemotherapy dose reductions (44% versus 13%, p=0.005), grade 3–4 non-haematological toxicities (41% versus 16%, p=0.043) and hospitalisations (54% versus 24%, p=0.016). ConclusionNo effect of iscador could be found on quality of life or total adverse events. Nevertheless, chemotherapy dose reductions, severe non-haematological side-effects and hospitalisations were less frequent in patients treated with iscador, warranting further investigation of iscador as a modifier of chemotherapy-related toxicity.

A Cautionary Tale: Dosing Chemotherapy in Infants With Retinoblastoma

A Cautionary Tale: Dosing Chemotherapy in Infants With Retinoblastoma

Venous thromboembolic events (VTE) in patients treated with cisplatin as compared to carboplatin-containing regimens.

e19679 Background: Data regarding the prevalence of venous thromboembolic events (VTE) with cisplatin-containing regimens has recently gained prominence. Cisplatin is an important chemotherapy agen...

Primary Diaphragmatic Yolk Sac Tumor and Review of the Literature

Primary yolk sac tumor of the diaphragm in children is very rare, and diagnosis of a diaphragmatic tumor poses challenges to clinical physicians. Here, we report a primary diaphragmatic yolk sac tumor in a 9-month-old girl, together with a review of 4 earlier reported cases in the English literature. Carboplatin-containing regimen successfully decreased the tumor size and a total resection of the tumor was made subsequently. The patient was disease-free 8 months after the completion of treatment.

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.

A phase Ib dose-escalation study of orally administered MP-470, a multi-kinase inhibitor and supressor of Rad51, in combination with carboplatin doublet containing regimens shows activity in highly refractory solid tumor patients

e13511 Background: MP-470 (MP) is an oral multi-targeted tyrosine kinase inhibitor which inhibits a number of validated tumor targets including c-kit, flt3, and PDGFα. MP470 targets cancer cells by disrupting DNA repair, an important survival pathway in many human cancers. Results presented herein are from two arms of a phase-Ib five arm trial of MP combined with standard of care (SOC) anti- cancer therapies. Methods: MP is administered in combination with SOC in a 21-day cycle. Adults with ECOG PS of 0–2 and malignant disease appropriate for SOC regimens consisting of paclitaxel/carboplatin (PC), carboplatin/etoposide (CE), topotecan, docetaxel, and erlotinib were enrolled. Each arm follows a 3+3 design where MP is escalated based on the modified Fibonacci sequence until the MTD of MP in combination with SOC agents is reached. RECIST and CTCAE are utilized to assess response and safety, respectively. The primary objectives of the study are to determine the MTD, DLTs, and quantify the effects of MP on the PK of SOC agents. Results: Between Dec 2007 and Aug 2008, 26 subjects were enrolled in the PC and CE arms and received a total of 70 cycles (median 2; range, 0–8) of MP at 4 dose levels (100–500 mg/day). Median number of prior therapies was 2 (range, 0–19). Male/Female: 14/12. Median age, 56 years (range, 24–76). Subjects completing ≥ 6 and ≥ 4 cycles were 5 and 7, respectively. Six PRs (2 neuroendocrine, 2 SCLC, 1 NSCLC, 1 small cell of anal canal) and 3 SDs (≥ 4 cycles) was observed. The MTDs have not been reached and DLTs have not been identified. Adverse events occurring in ≥ 15% of patients were myelosuppression, diarrhea, constipation, nausea, reflux, fatigue, alopecia, rash, neuropathy, anorexia, hypokalemia, dyspnea, and myalgias. MP470 did not alter the kinetics of SOC agents. Dose escalation in the PC and CE arms is ongoing. Conclusions: MP470 combined with carboplatin-containing regimens may promote tumor regression and may also sensitize/resensitize tumors to the anticancer effects of such agents. An amendment will be issued to collect tumor tissue biopsy at baseline and during treatment to adequately evaluate DNA damage in tumor tissue. [Table: see text]

Gemcitabine and Carboplatin Treatment in Advanced NSCLC: A Retrospective Evaluation Including Elderly Patients

Carboplatin-containing regimens are sometimes preferred for patients with advanced non-small cell lung cancer. Eighty-three patients with stage III-IV non-small cell lung cancer received 3 to 4 cycles of carboplatin AUC 5 on day 2 and gemcitabine 1250 mg/m2 on days 1 and 8 every 21 days. The overall response rate was 43.4%. Results obtained from elderly and non-elderly groups were compared using the logrank method. Median overall survival and progression-free survival were 11 and 7 months, respectively (12 and 7 months, non-elderly group; 6.5 and 5 months, elderly group, P = 0.28 and 0.25 respectively). Grade 3-4 toxicity included neutropenia, thrombocytopenia, anemia, nausea/vomiting, and diarrhea. Incidences of grade 3-4 toxicity were similar for elderly and non-elderly patients. Data confirm that carboplatin-gemcitabine is an active and well-tolerated regimen in advanced non-small cell lung cancer and could be investigated in elderly patients.

Hearing Loss in Pediatric Oncology Patients Receiving Carboplatin-containing Regimens

Carboplatin is a well-established chemotherapeutic agent used to treat a variety of pediatric malignancies. Platinum analogues such as cisplatin are known to be ototoxic, but little is known regarding the ototoxicity of carboplatin. We performed a single institution retrospective chart review of pediatric oncology patients who received platinum-containing regimens from 1993 to 2002. Ninety-nine patients with sufficient medical and audiologic data were identified. Significant hearing loss was defined as a Brock grade 1 or higher. The incidence was compared among 3 treatment groups (carboplatin only, carboplatin and cisplatin, and cisplatin only). Significant hearing loss in patients receiving carboplatin only was rare, observed in only 1/25 (4%) of patients. In contrast, 19/27 (70%) of patients receiving carboplatin and cisplatin possessed significant hearing loss, as did 27/47 (57%) of those patients receiving cisplatin only P<0.001. The difference in hearing loss could not be explained by different cumulative exposures of the platinum agents. Carboplatin, when used without cisplatin, is rarely associated with severe hearing loss, even at high cumulative doses.

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.