BACKGROUNDThe goals of the current study were to examine the incidence and severity of toxicity resulting from dexamethasone and prednisone during induction therapy for children with precursor B‐cell acute lymphoblastic leukemia (ALL) and to determine whether the addition of daunomycin affected toxicity.METHODSMedical records of patients with precursor B‐cell ALL from January 1996 through June 2000 were reviewed retrospectively for toxicity during the 4‐week induction phase and the 2 weeks after the induction phase.RESULTSOne hundred seventy‐six patients age < 14 years were diagnosed with precursor B‐cell ALL from January 1996 through June 2000. Of the 156 evaluable patients, 106 were treated with prednisone and 50 with dexamethasone. Fifty‐two patients received steroids, L‐asparaginase, and vincristine, whereas 104 high‐risk patients received daunomycin in addition to these 3 agents. The incidence of gastritis was significantly higher among patients receiving dexamethasone (P = 0.01); incidence rates of hyperglycemia, hypertension, and myopathy were similar for all treatment groups. Dexamethasone led to more weight gain than did prednisone (+11.9% vs. +5.4%; P = 0.002). Serious infections were observed in 27 (25.5%) and 18 (36%) patients receiving prednisone and dexamethasone, respectively (P ≤ 0.2). Five patients, four of whom received prednisone and one of whom received dexamethasone, died of infection. The addition of daunomycin to treatment regimens increased overall toxicity (P < 0.01). When daunomycin was included in treatment regimens, toxicity was greater among patients receiving dexamethasone; in contrast, when daunomycin was not included, toxicity was equal for both treatment groups. Regardless of daunomycin use, there was no difference in the incidence of serious infection between the two groups. ALL treatment was not compromised by steroid‐related toxicity in either group.CONCLUSIONSThe addition of daunomycin led to a much larger increase in dexamethasone‐related toxicity compared with the increase in prednisone‐related toxicity. Although the use of daunomycin enhanced dexamethasone‐related toxicity, this enhancement did not result in a higher mortality rate or the alteration of planned ALL therapy. Cancer 2003;97:2898–903. © 2003 American Cancer Society.DOI 10.1002/cncr.11390

STUDY OBJECTIVESTo compare breast cancer metastases between obese and nonobese women and to evaluate the effect of first-line metastatic chemotherapy in each group.METHODA retrospective study was performed in an educational institute in Ireland. The study consisted of two parts: the first part was a comparative analysis of metastases development in obese (arm A) and nonobese patients (arm B). The second part was a comparison between both arms in relation to their response to first-line metastatic chemotherapy and their survival data.RESULTSBetween 2009 and 2014, we reviewed 118 patients with metastatic breast cancer. All the patients fulfilled our inclusion criteria. In all, 48% of patients were obese and 52% were nonobese. There were no statistically significant differences between the two groups. For arms A and B, the median interval between initial cancer diagnosis and distant metastases development (distant metastases-free survival) was 5.8 versus 7.6 years, respectively (Pvalue 0.04). Earlier visceral (liver and lung) metastases were observed in obese compared to nonobese women (Pvalues were 0.05 and 0.04, respectively). The most commonly used chemotherapy was weekly paclitaxel. Our treatments showed significantly better treatment response and better survival results in nonobese women than in obese ones, who were premenopausal with performance state 2, pathological grade 3, and four or more positive lymph nodes.CONCLUSIONObesity is linked with visceral metastases development, especially lung and liver metastases. Furthermore, first-line metastatic chemotherapy achieved better results in nonobese patients.

Sildenafil citrate is the first oral treatment for erectile dysfunction. Its oral bioavailability is about 40%. This research investigated the intestinal transport parameters of sildenafil citrate in rabbit using an in situ intestinal perfusion technique. This was studied in four different anatomical sites, namely duodenum, jejunoileum, ascending colon and rectum. The results revealed the highest absorptive clearance in the jejunoileum. The values of the permeability area product normalized to segment length (ml/min.cm) were 0.0101, 0.0063, 0.0059 and 0.0023 and those of the percentage absorbed were 68.0, 32.3, 23.0 and 5.0 in jejunoileum, duodenum, ascending colon and rectum, respectively. The values of the length (cm) required for complete absorption were 87.6, 137, 153 and 384 for each anatomical site in the same order. The absorptive clearance did not correlate with the net water flux in the four anatomical regions studied, indicating a mainly passive diffusion mechanism through a transcellular pathway. The plasma sildenafil concentrations achieved during intestinal perfusion experiments and sildenafil total body clearance in the rabbit were used to calculate the fraction of sildenafil that reached the systemic circulation relative to the amount that disappeared from the intestinal segment. Only 34% of sildenafil that disappeared from the intestinal segment appeared in the systemic circulation indicating that the presystemic elimination of sildenafil is 66%. These results confirm that the incomplete bioavailability of sildenafil is mainly due presystemic elimination.

Cervical cancer is the second most common cancer in women. Neoadjuvant chemotherapy for patients with locally advanced cervix cancer has comparable benefits to concurrent chemoradiotherapy (CCRT), but with fewer side effects. This systematic review aims to provide a comprehensive summary of the benefits of neoadjuvant chemotherapy for the management of locally advanced cervix cancer from stage IB2 (tumor >4.0 cm) to IIIB (tumor extending to the pelvic wall and/or hydronephrosis). Our primary objective was to assess benefits in terms of survival. The data source included the USA national library of medicine, Medline search, and the National Cancer Institute PDQ Clinical Protocols. Inclusion criteria for consideration in the current systematic review included studies published between January 1997 and December 2012. In terms of histology, they had to be focused on squamous cell carcinoma, adenosquamous carcinoma, and/or adenocarcinoma. Patients should be either chemotherapy naïve or cervix cancer chemotherapy naïve, and have a performance status ≤2. The search in the above-mentioned scientific websites led to identify 49 publications, 19 of which were excluded, as they did not meet the inclusion criteria of this systematic review. Therefore only 30 studies were deemed eligible. Data was collected from 1760 patients enrolled in the current systematic review study. The mean age was 45.2 years. The mean tumor size was 4.7 cm. The most commonly used chemotherapies were cisplatin doublets. Paclitaxel was the most commonly used chemotherapeutic agent in the doublets. The mean chemotherapy cycles were 2.7. After chemotherapy, patients underwent surgery after a mean time of 2.5 weeks. The standard operation was radical hysterectomy with pelvic lymphadenectomy. Chemotherapy achieved an objective response rate of 84%. The 5-year progression-free survival and overall survival were 61.9% and 72.8% respectively. The treatment protocol was associated with a mild early toxicity profile. Leucopenia and neutropenia were the most common side effects. Late toxicity was also generally mild and mainly associated with bladder dysfunction and vaginal dehiscence. The quality of the studies was assessed using the Newcastle-Ottawa quality assessment scale. Neoadjuvant chemotherapy achieved comparable survival results to CCRT, and was associated with less toxicity.

Background: The primary objective of the study was to evaluate the long-term changes in ejection fraction (EF) associated with paclitaxel infusion. Methods: 50 patients were enrolled in this prospective study between 2011 and 2015. The study design included frequent follow-up visits to the clinic, EF evaluation at baseline, and regular EF assessment by echocardiography for 30 months after treatment. Results: The median baseline EF was 60% (95% confidence interval (CI) 50-80%). At 30 months, the median EF was 48% (95% CI 40-60%; p = 0.03). During the 30-month follow-up, 10 (20%) patients developed grade 1 and 2 cardiotoxicities; none developed grade 3 or 4 cardiotoxicities. Furthermore, paclitaxel cardiotoxicity increased among patients with high-risk features including associated diabetes mellitus, hypertension, prior radiotherapy to the chest wall, performance status of 2, and age > 60 years. Conclusion: Paclitaxel has cardiotoxic effects. Careful monitoring of cardiac function during and after paclitaxel infusion is required in patients with high-risk features.