In our cohort of ALL patients, BMI was elevated at diagnosis (mean standardized BMI z-score = 0.22, standard deviation = 1.4) then increased and remained elevated for the entire duration of chemotherapy. Children who were 2-9 years of age at diagnosis began therapy with a substantially lower BMI and remained lower over the course of chemotherapy than patients aged 10-18 years at diagnosis. It will be important for future investigations to explore the biological and behavioral factors that may underlie such differential patterns of BMI change over time.

Paclitaxel plus carboplatin is a moderately active regimen in patients with advanced NSCLC and warrants comparison with existing cisplatin-based regimens in a prospective randomized trial. The toxicities of this regimen are well tolerated in patients with a good PS.

Acute lymphoblastic leukemia (ALL), the most common malignancy in children, constitutes 25% of all pediatric cancer. Childhood cancer patients who are obese at diagnosis represent a particular challenge for the oncologist. Obesity may complicate chemotherapy dose determination, and has been associated with decreased overall and event-free survival in a number of adult cancer patients, and more recently in pediatric patients. The purpose of the present study was to examine whether obesity at diagnosis was associated with decreased overall and event-free survival in a cohort of 322 predominantly Hispanic pediatric patients with B-precursor ALL. Obesity was classified as an age-standardized and sex-standardized body mass index z-score at or above the 95th percentile. Hazard ratios (HRs) for overall and event-free survival were assessed using Cox proportional hazards regression modeling. Obesity at diagnosis was not associated with decreased overall survival (HR = 1.40, 95% confidence interval = 0.69-2.87) or event-free survival (HR = 1.08, 95% confidence interval = 0.65-1.82) in the overall cohort or in either of the 2 age-at-diagnosis (2 to 9 y; 10 to 18 y) subgroups. Our finding of no obesity-related prognostic effect in the overall cohort and in the under 2 to 9-year age-at-diagnosis cohort was consistent with the previous large-scale study of ALL patients; the absence of a prognostic effect in the 10 to 18-year age-at-diagnosis cohort, however, conflicted with previous findings.

BACKGROUND The objective of this study was to examine changes over time in body mass index (BMI) from diagnosis through chemotherapy for pediatric patients with B‐precursor acute lymphoblastic leukemia (ALL). METHODS The study cohort consisted of 141 white Hispanic pediatric patients who were diagnosed with ALL and were treated at 2 South Texas pediatric oncology centers between 1993 and 2002. Changes in age‐standardized and gender‐standardized BMI scores were assessed. RESULTS The study cohort exhibited a steady increase in age‐adjusted and gender‐adjusted BMI scores for the first 12 months of therapy, a modest increase in BMI scores during the 18–23 month and 24–29 month periods, followed by a slight decrease in BMI scores at 30 months (end of therapy). A repeated‐measures analysis indicated significant effects for time (P = 0.019) and time by baseline BMI category interaction (P = 0.0001) but no significant interaction effect between time and gender (P = 0.65). CONCLUSIONS Although it is known that leukemia therapy is associated with prevalent obesity in survivorship, its pattern of development during therapy has not been elucidated. In the current cohort of Hispanic children with ALL, BMI scores were elevated at diagnosis (mean ± standard deviation standardized BMI Z score, 0.33 ± 1.4), then increased, and remained elevated for the entire duration of chemotherapy. Patients who were classified as normal weight exhibited an increase in BMI over time; patients who were classified as overweight at diagnosis exhibited BMI patterns that were relatively stable; and patients who were classified as obese exhibited a very slight decline over time. These findings suggest that the risk for chemotherapy‐related weight gain applies predominantly to children who begin ALL therapy within a normal weight range. Cancer 2005. © 2005 American Cancer Society.

Summary:lowing initial surgery and chemotherapy are rarely cured of their disease by subsequent treatment. 8 Analyses of the utility of dose-escalation of chemotherapeutic agents withThe purpose of this study was to develop a high-dose chemotherapy (HDC) and peripheral blood stem cell out hematopoietic stem cell support in patients with advanced ovarian cancer have produced conflicting (PBSC) regimen for treatment of patients with ovarian carcinoma that could be administered in an outpatient results. 4,9-12High-dose chemotherapy (HDC) followed by the setting. Fourteen patients with advanced ovarian (n = 9) or breast (n = 5) carcinoma, who had failed conveninfusion of autologous hematopoietic stem cells consistently produces high response rates in patients with tional chemotherapy, were entered into a dose-escalation trial to determine the maximum tolerated dose advanced ovarian carcinoma who have failed chemotherapy; however, these responses are usually of short dur-(MTD) of carboplatin that could be administered with fixed doses of melphalan (160 mg/m 2 ) and mitoxantrone ation with long-term survival in 10-25% of patients. 13-21High-dose melphalan followed by bone marrow infusion (50 mg/m 2 ). Twenty-five additional patients were included in a phase II trial at the MTD. Two of two was evaluated in 14 patients with stage III-IV ovarian carcinoma who were positive microscopically or macropatients had grade 4 severe regimen-related toxicities (RRT), one fatal, at a dose level of 1600 mg/m 2 . Two of scopically at second-look laparotomy. 22 Five of these 14 patients (37%) were alive and disease-free 30-60 months 29 patients (6.9%) treated at the MTD (carboplatin, 1400 mg/m 2 ) died of RRT. All three patients who died after treatment, suggesting benefit from early intervention with HDC. 22of toxicity had a calculated AUC for carboplatin Ͼ30 mg/ml/min. Thirty-one patients with ovarian cancer More recently, HDC has been utilized as consolidation for patients with advanced ovarian carcinoma who who had failed chemotherapy were treated, 24 at the MTD. Fourteen of 20 patients (70%) with ovarian carciresponded to initial therapy. 23,24 However, the impact of HDC as consolidation therapy will only be known when noma with evaluable disease achieved a CR and seven (35%) are alive disease-free a median of 20 months appropriate randomized trials are performed. Although several HDC regimens requiring hematopoietic (range, 7-26). Five of seven patients with ovarian cancer who had failed chemotherapy but were rendered clinistem cell support have been evaluated in patients with advanced ovarian carcinoma, no regimen has emerged cally disease-free following surgery survive without progression a median of 13 months (range, 9-19). Eight of which is clearly superior. Melphalan is an ideal agent to incorporate into a high-16 (50%) platinum-resistant and 4/12 (33%) platinumsensitive patients with ovarian cancer survive diseasedose treatment regimen for patients with ovarian carcinoma because of ease of administration, demonstrated ac...

BACKGROUND The objective of the current study was to compare chemotherapy dose modifications in obese (a body mass index [BMI] > 95%) and nonobese (a BMI ≤ 95%) pediatric patients with acute lymphoblastic leukemia (ALL). METHODS The study cohort was comprised of 199 pediatric patients diagnosed with ALL who were treated at 1 of 2 South Texas pediatric oncology centers between 1990–2000. The relative chemotherapy dose modification during the induction phase of chemotherapy was calculated as the ratio of 1) the actual administered dose of L‐asparaginase and 2) the protocol‐calculated dose of L‐asparaginase. The extent to which the chemotherapy dose modification varied according to obesity status was assessed using stratified Student t tests and an ordinary least‐squares regression analysis. RESULTS Obese ALL patients were found to exhibit a 7% decrease in the mean relative modification of L‐asparaginase during induction chemotherapy compared with their nonobese counterparts. This finding was statistically significant (P = 0.009), even after adjustment for gender, age, ethnicity, and clinical institution. CONCLUSIONS To the authors' knowledge, the current study is the first published report of an obesity‐associated chemotherapy dose modification in pediatric patients with ALL, the most common childhood malignancy. It will be important to examine whether these findings are consistent with those observed in future studies, and ultimately to assess the association between obesity‐related dose modifications and long‐term cancer outcomes. Cancer 2005. © 2005 American Cancer Society.

9517 Background: Cisplatin is one of the most effective agents against osteosarcoma. Cisplatin is usually administered as a short IV infusion in most contemporary North American osteosarcoma treatment protocols. Ototoxicity from such protocols has not been well defined. The aim of this study was to determine the incidence and the risk factors for hearing loss in children with osteosarcoma. Methods: Eligible patients (pts) in this retrospective cohort study had osteosarcoma diagnosed and treated at our center from 1/1/1995 to 12/31/2004, were 3–18 years of age at diagnosis, and had a normal audiogram prior to the start of chemotherapy. All pts received cisplatin according to either standard practice or current open protocol. Most regimens prescribed a cumulative dose of 480 mg/m2 over 4 cycles. Pts with hearing loss at lower doses had cisplatin held on an individualized basis. Hearing was evaluated using pure-tone audiometry prior to the start of therapy, before each cycle of cisplatin administration, and off-therapy. The primary endpoint was any hearing loss as defined as > 20 dB decrease in hearing above 4,000 Hz. Fisher's exact test and logistic regression methods were used to identify univariate and independent predictors of hearing loss, respectively. Results: The incidence of hearing loss was 16/40 (40%). Six pts discontinued cisplatin early due to hearing loss. Seven of 9 pts (77.8%) who received cisplatin 120 mg/m2 as a short IV infusion on 1 day developed hearing loss compared to 9 of 31 (29.0%) pts who received this same dose as two daily infusions (p=0.018). On univariate analyses, age and cumulative cisplatin dose were not predictive of hearing loss. Logistic regression controlling for age, sex, race, and cumulative dose showed that administration of cisplatin 120 mg/m2 on 1 day compared to 2 days was an independent predictor of hearing loss (odds ratio of 11.6, 95% confidence interval = 1.62–82.87). Conclusions: Cisplatin given as 120 mg/m2/dose on 1 day was associated with greater risk of hearing loss than 60 mg/m2/dose on 2 days. Cumulative dose and age were not found to be predictors of hearing loss in this relatively small cohort. No significant financial relationships to disclose.

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