A Phase 2 trial of the liposomal DACH platinum L-NDDP in patients with therapy-refractory advanced colorectal cancer

Purpose: L-NDDP (Aroplatin^TM) is a liposomal formulation of cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexane platinum (II), a structural analogue of oxaliplatin. In a Phase 1 trial, the maximum tolerated dose (MTD) of L-NDDP was 312.5 mg/m² with myelosuppression as dose limiting toxicity (DLT). We conducted a Phase 2 trial of L-NDDP in patients (pts) with advanced colorectal cancer (CRC) refractory to 5-fluorouracil/leucovorin or capecitabine and irinotecan to investigate the anti-tumor response of L-NDDP and to further characterize its toxicity profile in this population. Methods: L-NDDP was administered intravenously, once every 28 days. The starting dose was 300 mg/m², with possible intra-patient dose escalation in the absence of grade 2 or higher drug-related toxicity. Patients were treated until disease progression or unacceptable toxicity. Of 20 eligible patients all were evaluable for toxicity and 18 were evaluable for response. Hematologic toxicities included anemia (grades 1–4) in 20% of pts and leucopenia, neutropenia and thrombocytopenia (grade 1/2) in 5% of patients each. Common non-hematologic toxicities included nausea (75%), vomiting (60%), and fatigue (70%), reversible infusion reactions (chest/back pain or shortness of breath; 40%), transient transaminase elevations (35%) and hyperbilirubinemia (20%). Grade 3–4 toxicities included infusion reaction (20%), vomiting (15%), fatigue (15%), anemia (10%) and ALT/AST elevation (5/15%). Peripheral neuropathy (grade 1/2) was seen in 15% of pts. One of 18 pts had a confirmed PR (5.6%), three (16.7%) had stable disease (≥3 months) and 14 pts progressed. L-NDDP was well tolerated in this group of refractory patients and demonstrated evidence of anti-tumor activity. Conclusion: Further studies of L-NDDP, preferably in combination with other agents such as fluoropyrimidines, are warranted.     

Knowledge and use of folic acid in Croatian pregnant women--a need for health care education initiative

Adequate periconceptional folic acid (FA) intake reduces the risk of neural tube defects. There are still no official FA supplementation guidelines, FA fortification policies or larger studies of awareness regarding FA or number of planned pregnancies in Croatia. This study assesses the knowledge and practice regarding FA supplementation and reports the trends in pregnancy planning in Croatia. A total of 569 pregnant women completed an anonymous questionnaire and about 72% of them were aware of the benefits of FA. Despite 75.53% of planned pregnancies, only 14.41% of all women took FA appropriately. Croatian women get information about FA from the media, health professionals and friends, but 63.77% got this information too late. The present study showed low percentage of appropriate FA intake despite high number of planned pregnancies in Croatia. It emphasizes the need for immediate and continuous public health education initiative about FA intake targeted to the women of childbearing age before their pregnancies have occurred.     

Influence of calcium on the action of Vipera ammodytes ammodytes snake venom on the myocardium

V. ammodytes ammodytes snake venom produced irreversible block of the isolated, artificially stimulated rat right ventricle or isolated rat heart. This was the result of degenerative changes of the myocardium caused by the direct effect of toxic components of the venom. An excess of Ca²⁺ could temporarily restart the contractions.     

Initial treatment of temporomandibular joint osteoarthritis

The diagnostic procedure and the initial treatment of a female patient suffering from temporomandibular disorder is described. Osteoarthritis and the discopathy of the temporomandibular joint were diagnosed both clinically and by magnetic resonance imaging. Anxiety was confirmed by measuring instrument State-Trait Anxiety Inventory. Pains in temporomandibular joints were removed after the initial treatment in which the occlusion splint had been used so that conditions for carrying out the definite occlusal treatment were fulfilled.     

Folding valvuloplasty without leaflet resection: simplified method for mitral valve repair

Standard repair techniques can prove challenging in patients with severe myxomatous mitral valve disease when there is a broad-based mid-portion of the posterior leaflet and small medial and lateral scallops. We describe a new surgical technique in which the mitral valve repair was accomplished by simple folding the prolapsed segment of the posterior leaflet and by insertion of the flexible annuloplasty ring.     

Concomitant chemobrachyradiotherapy with ifosfamide and cisplatin followed by consolidation chemotherapy in locally advanced squamous cell carcinoma of the uterine cervix: results of a phase II study

PURPOSE: To evaluate the efficacy and toxicity of ifosfamide and cisplatin administered concomitantly with low-dose-rate brachytherapy followed by consolidation chemotherapy in the treatment of locally advanced squamous cell cervical carcinoma (LASCC). METHODS AND MATERIALS: Forty-four patients with biopsy-proven LASCC were enrolled. FIGO Stages IB2 bulky to IVA were entered into this study. Patients were assigned to receive external radiotherapy (50 Gy in 25 fractions); then ifosfamide 2 g/m(2) plus cisplatin 75 mg/m(2) was applied during two low-dose-rate brachytherapy applications, and 4 cycles of consolidation chemotherapy with the same drug combination were given after completion of radiotherapy. The planned dose to point A was 85 Gy. RESULTS: All patients received both courses of concomitant chemobrachytherapy and at least 1 cycle of consolidation chemotherapy. The average duration of radiation was 45.1 days. The clinical complete response rate was 100%. Grade 3 and 4 leukopenia occurred in 25% and 11% of the cycles, respectively. After a median follow-up of 34 months (range, 20-54 months), the recurrence-free and the overall survival rates were 84% and 91%, respectively. Major delayed local complications occurred in 7 cases (16%). CONCLUSIONS: These results indicate that concomitant chemobrachyradiotherapy with ifosfamide and cisplatin is a feasible combination for patients with LASCC of the cervix uteri. A randomized trial is planned.     

Sexual behaviour of Croatian blood donors as a threat to the health of blood recipients

Background

In this cross-sectional study we assessed the prevalence of the various blood safety sexual risk behaviours among blood donors from East Croatia and the possibilities for improving the present blood donor screening procedure.

Materials and methods

The study included 423 blood donors of both sexes who completed a specially designed anonymous questionnaire immediately after their blood donations. The questionnaire contained questions on demographic data, sexual preferences, and possible sexual risk behaviours in the period before the blood donation.

Results

The study revealed that the most common forms of sexual risk behaviour among Croatian blood donors had been irregular condom use during sexual contacts with new partners (294/423; 69.5%) and five or more sexual partners during the lifetime (213/423; 50.4%). More male than female subjects had had five or more sexual partners during their lifetime (p<0.0001). Compared to married donors, single subjects more frequently reported sexual contacts without using a condom with their new partners in the period from the last blood donation (p<0.0001) and also in the period of 1 month before current blood donation (p=0.0060). A larger number of younger than older subjects had practiced different types of sexual intercourses during the lifetime (p=0.0002) but more older than younger subjects reported irregular use of condom on sexual contacts with a new partner during their lifetime (p=0.0231).

Conclusion

Blood donors who were involved in various forms of sexual risk behaviour represent a serious threat to the health of blood recipients. In this respect a new approach to blood donor screening procedure with additional questions on sexual behaviour in anonymous donor questionnaires would improve the safety of transfusion treatment in East Croatia.     

Renal tumor with tumor thrombus in inferior vena cava and right atrium: the report of five cases with long-term follow-up

Objective  

To evaluate early and long-term results of radical surgical removal of renal cell cancer (RCC) with tumor thrombus (TT) in the inferior vena cava (IVC) and right atrium (RA).