Investigational therapies currently in Phase II clinical trials for the treatment of pelvic serous carcinomas

Introduction: Pelvic serous carcinomas (PSCs) are a controversial entity, which mostly comprise fallopian tube carcinoma (FTC), primary peritoneal carcinoma (PPC) and serous ovarian carcinoma (OC). Despite incremental attention towards understanding pelvic serous carcinogenesis, the gold standard treatment and survival rates have not substantially changed in these last decades.

Areas covered: This review summarizes and gives a critical overview of the ongoing Phase II trials investigating therapies for PSC.

Expert opinion: Several novel molecules have been developed and are currently under investigation for the treatment of PSC, including FTC, PPC and serous OC. The trend of novel targeted agents is one towards individualized, tailored therapy, based on the molecular and biological differences that characterize tumors that seem similar based solely on histological analysis. The task of developing new molecules is particularly difficult for PSC, given the recurrent development of new patterns of drug resistance. However, even if current research is focused towards identifying the best treatments for each woman with a molecularly defined disease, a deeper knowledge of the molecular biology and genetics underlying FTC and its relation as a precursor of PSC is needed.     

Plasmodium falciparum chloroquine and quinine sensitivity in asymptomatic and symptomatic children in São Tomé Island

Plasmodium falciparum sensitivity to quinine in São Tomé was determined by in vivo and in vitro tests in 56 children with mild or cerebral malaria. Chloroquine sensitivity was assessed by in vitro tests in 105 parasitaemic asymptomatic children from the same community as the cases. The WHO standard methodology was used. No resistance to quinine was found by in vivo or in vitro tests in either group of patients or in asymptomatic children, although some degree of chloroquine resistance was found with the in vitro test. This was more common in patients than in asymptomatic children. Chloroquine resistance may be explained by the recent history of malaria in São Tomé Island, which caused an important decrease of immunity among the population and consequently the emergence of resistant strains. Implications of the use of in vivo / in vitro tests for determining the antimalarial drug policy within the primary health care system are discussed.     

Radioiodine treatment with 30 mCi after recombinant human thyrotropin stimulation in thyroid cancer: effectiveness for postsurgical remnants ablation and possible role of iodine content in L-thyroxine in the outcome of ablation

The main steps in the management of differentiated thyroid cancer are thyroidectomy, treatment with iodine-131 ((131)I), and follow-up with whole-body scanning (WBS) and serum thyroglobulin (Tg) determination. Both (131)I treatment and follow-up require maximum stimulation of normal or pathological thyroid remnants by TSH. The use of recombinant human TSH (rhTSH) has been shown to be useful for follow-up, whereas previous reports are not univocal regarding the use of (131)I postsurgical ablation of thyroid remnants, at least when low doses (30 mCi) of (131)I are administered. A possible explanation for the diminished effectiveness of (131)I treatment after rhTSH may be the interference of iodine content of L-thyroxine (L-T4) therapy during the protocol of administration of rhTSH. We have evaluated the effectiveness of stimulation by rhTSH for radioiodine ablation of postsurgical remnants, stopping L-T4 the day before the first injection of rhTSH and restarting L-T4 the day after (131)I. The study included two groups of patients: group 1 included 16 patients with differentiated thyroid cancer (15 papillary cancers and 1 follicular cancer, stages I and II), who were treated with 30 mCi (131)I with the aid of rhTSH, using the standard protocol but stopping L-T4 as stated previously; and group 2 included 24 patients with the same features (histology and stage) of disease treated with 30 mCi in the hypothyroid state after L-T4 withdrawal. In both groups, serum TSH reached a very good stimulation level [76-210 U/liter (mean, 112 +/- 11 SE) and 38-82 U/liter (mean, 51 +/- 3 SE), respectively]. At the first WBS (after (131)I treatment), all patients showed thyroid remnants. Furthermore, two patients of the first group and three patients of the second group showed lymph node metastases. After 1 yr, all patients were studied again and underwent WBS with a tracer dose of (131)I and serum Tg measurement using rhTSH with the same protocol in both groups. The percentage of ablation (undetectable Tg and a negative WBS) was higher, although not reaching statistical significance, in patients treated with rhTSH: 81.2% in patients treated by rhTSH withdrawal and 75.0% in patients treated by L-T4 withdrawal, respectively. No patient experienced symptoms of hypothyroidism during the 4 d of L-T4 interruption, and serum T4 remained in the normal range. Urinary iodine was analyzed in both groups and compared with a control group of patients who received, for diagnostic purposes, rhTSH without stopping L-T4. In the first group, urinary iodine was 47.2 +/- 4.0 microg/liter (mean +/- SE; P = 0.21 vs. the second group, P = 0.019 vs. control group). In the second group, urinary iodine was 38.6 +/- 4.0 microg/liter (mean +/- SE; P < 0.001 vs. control group); urinary iodine in the control group was 76.4 +/- 9.3 microg/liter (mean +/- SE). Our data show that rhTSH, as administered in the protocol stated previously, allows at least the same rate of ablation of thyroid remnants when low doses (30 mCi) of (131)I are used. The possible role of interference of iodine content in L-T4 is not surprising if we consider that the amount of iodine in 30 mCi is negligible (5 microg) compared with the amount of iodine content in a daily dose of T(4) ( approximately 50 microg). The cost of rhTSH seems modest compared with the high cost of complex therapeutic regimens in other areas of oncology and in consideration of the well-being of patients and of the high level of effectiveness of the treatment.     

Clinical and haematological improvement induced by etidronate in a patient with idiopathic myelofibrosis and osteosclerosis

Summary We report a patient with agnogenic myeloid metaplasia associated with debilitating bone pain due to increased bone turnover and osteosclerosis. Treatment with etidronate at a dose of 6 mg/kg per day on alternate months resulted in a complete recovery of bone symptoms and normalization of metabolic parameters of bone turnover; unexpectedly, a sustained haematological improvement was also observed after several months of therapy, suggesting that bone marrow microenvironment improvement was able to restore a nearly normal haemopoiesis. We suggest that diphosphonate therapy may be of value in patients with AMM and increased bone turnover.     

A multimedia consent tool for research participants in the Gambia: a randomized controlled trial

ObjectiveTo assess the effectiveness of a multimedia informed consent tool for adults participating in a clinical trial in the Gambia.MethodsAdults eligible for inclusion in a malaria treatment trial (n = 311) were randomized to receive information needed for informed consent using either a multimedia tool (intervention arm) or a standard procedure (control arm). A computerized, audio questionnaire was used to assess participants’ comprehension of informed consent. This was done immediately after consent had been obtained (at day 0) and at subsequent follow-up visits (days 7, 14, 21 and 28). The acceptability and ease of use of the multimedia tool were assessed in focus groups.FindingsOn day 0, the median comprehension score in the intervention arm was 64% compared with 40% in the control arm (P = 0.042). The difference remained significant at all follow-up visits. Poorer comprehension was independently associated with female sex (odds ratio, OR: 0.29; 95% confidence interval, CI: 0.12–0.70) and residing in Jahaly rather than Basse province (OR: 0.33; 95% CI: 0.13–0.82). There was no significant independent association with educational level. The risk that a participant’s comprehension score would drop to half of the initial value was lower in the intervention arm (hazard ratio 0.22, 95% CI: 0.16–0.31). Overall, 70% (42/60) of focus group participants from the intervention arm found the multimedia tool clear and easy to understand.ConclusionA multimedia informed consent tool significantly improved comprehension and retention of consent information by research participants with low levels of literacy.     

Combining electromagnetic navigation and 3‐D mapping to reduce fluoroscopy time and achieve optimal CRT response

Implantation of cardiac resynchronization therapy (CRT) devices can be challenging, time consuming, and associated with high‐dose x‐ray exposure. We present the technique in which an electromagnetic navigation system (MediGuideTM, St. Jude Medical) and an electroanatomical three‐dimensional mapping system (EnSite NavX, St Jude Medical) are usefully combined for implanting implantable cardioverter defibrillator CRT devices with strong reduction of x‐ray exposure, and for targeting the most delayed regions in the activation maps avoiding scars for optimal CRT response.     

The impact of childhood vaccines on bacterial carriage in the nasopharynx: a longitudinal study

Background

There is increasing evidence that childhood vaccines have effects that extend beyond their target disease. The objective of this study was to assess the effects of routine childhood vaccines on bacterial carriage in the nasopharynx.

Methods

A cohort of children from rural Gambia was recruited at birth and followed up for one year. Nasopharyngeal swabs were taken immediately after birth, every two weeks for the first six months and then every other month. The presence of bacteria in the nasopharynx (Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus) was compared before and after the administration of DTP-Hib-HepB and measles-yellow fever vaccines.

Results

A total of 1,779 nasopharyngeal swabs were collected from 136 children for whom vaccination data were available. The prevalence of bacterial carriage was high: 82.2% S. pneumoniae, 30.6%, S.aureus, 27.8% H. influenzae. Carriage of H. influenzae (OR = 0.36; 95% CI: 0.13, 0.99) and S. pneumoniae (OR = 0.25; 95% CI: 0.07, 0.90) were significantly reduced after measles-yellow fever vaccination; while DTP-Hib-HepB had no effect on bacterial carriage.

Conclusions

Nasopharyngeal bacterial carriage is unaffected by DTP-Hib-HepB vaccination and reduced after measles-yellow fever vaccination.