Weekly cisplatin and daily oral etoposide is highly effective in platinum pretreated ovarian cancer

We investigated the potential of weekly cisplatin and daily oral etoposide followed by oral etoposide maintenance therapy in patients with platinum-refractory ovarium cancer. One hundred and seven patients were entered on the study, 98 patients completed the induction therapy consisting of cisplatin at either 50 or 70 mg m−2 weekly for six administrations plus oral etoposide at a dose of 50 mg daily. Of these 98 patients, 38 had a platinum treatment-free interval of more than 12 months, 32 had an interval between 4 and 12 months, and 28 had progressed during or within 4 months after last platinum therapy. We assessed response rates and time to progression, and also response duration and survival. Analyses were done on the 98 evaluable patients. All 107 patients were considered evaluable for toxicity. Of the 38 patients with a treatment-free interval of more than 12 months, 92% responded, with 63% complete responses. The median progression-free survival in these patients was 14 months, and the median survival was 26 months. Of the 32 patients with an interval of 4–12 months, 91% responded, with 31% complete responses, a median progression-free interval of 8 and a median overall survival of 16 months. Of the 28 patients with platinum-refractory disease, 46% as yet responded, with 29% complete responses, median progression-free interval of 5 and an overall survival of 13 months. Haematologic and non-haematologic, particularly renal toxicity and neurotoxicity, were notably mild. We conclude that this intensive regimen of weekly cisplatin plus daily etoposide is highly effective and well tolerated in patients with ovarian cancer relapsing after conventional platinum-based combination chemotherapy, including patients who have progressed during or within 4 months after platinum treatment

Erufosine, a novel alkylphosphocholine, in acute myeloid leukemia: single activity and combination with other antileukemic drugs

Alkylphosphocholines represent a new class of cytostatic drugs with a novel mode of action. Erufosine (ErPC3), the first compound of this class that can be administered intravenously, has recently been shown to be active against human tumor and leukemic cell lines. METHODS: In order to evaluate the antileukemic potential of ErPC3 in acute myeloid leukemia (AML) the lethal concentration 50% (LC 50) was determined using WST-1 assay. For analysis of cell death, staining for Annexin V and activated caspase 3 was performed. An interaction analysis was performed by calculation of combination index and construction of isobolograms. RESULTS: The LC 50 was 7.4 microg/ml after 24 h and 3.2 microg/ml after 72 h in HL 60 cells and 30.1 and 8.6 microg/ml, respectively, in 19 fresh samples from patients with AML. ErPC3 was found to be cytotoxic in HL60 cells with distinct activation of caspase 3. ErPC3 was not cross-resistant with cytarabine, idarubicine and etoposide as shown by the linear relation of respective LC 50s. The latter agents, however, exerted an additive cytotoxicity in combination with ErPC3 as revealed by isobologram analysis and combination index, although results are uneven for idarubicine. CONCLUSION: Based on these data ErPC3 appears as a novel antileukemic candidate drug, which needs to be explored further in the treatment of AML

Cisplatin neurotoxicity in the treatment of metastatic germ cell tumour: time course and prognosis

In order to ascertain the incidence and prognosis of cisplatin-induced neurotoxicity in testis cancer patients undergoing combination chemotherapy, 29 patients with metastatic disease were studied prospectively. Assessments included enquiry into neurological symptoms, measurement of sural nerve sensory action potential and conduction velocity, and vibration threshold in the left big toe. At the end of chemotherapy (3 to 4 cycles) only 3 out of 26 (11%) patients had paraesthesiae, but 3 months later the proportion rose to 65%. Resolution occurred in the majority over the ensuing 12 months so that only 17% had persistent symptoms. None of the 11 patients treated with 3 cycles of chemotherapy had persisting symptoms. Vibration thresholds showed a significant deterioration during chemotherapy (P = 0.032), further deterioration in the 3 months following chemotherapy (P = 0.009) and significant improvement between 3 and 12 months after chemotherapy (P = 0.038). Sural nerve sensory action potentials and conduction velocities were unhelpful.© 2001 Cancer Research Campaignhttp://www.bjcancer.co

Chemotherapy for malignant pleural mesothelioma: past results and recent developments

PubMedWo

Improving word reading speed: Individual differences interact with a training focus on successes or failures

Contains fulltext : 101028.pdf (publisher's version ) (Open Access) Contains fulltext : 101028-erratum.pdf (publisher's version ) (Open Access)The effect of two training procedures on the development of reading speed in poor readers is examined. One training concentrates on the words the children read correctly (successes), the other on the words they read incorrectly (failures). Children were either informed or not informed about the training focus. A randomized controlled trial was conducted with 79 poor readers. They repeatedly read regularly spelled Dutch consonant–vowel–consonant words, some children their successes, others their failures. The training used a computerized flashcards format. The exposure duration of the words was varied to maintain an accuracy rate at a constant level. Reading speed improved and transferred to untrained, orthographically more complex words. These transfer effects were characterized by an Aptitude-Treatment Interaction. Poor readers with a low initial reading level improved most in the training focused on successes. For poor readers with a high initial reading level, however, it appeared to be more profitable to practice with their failures. Informing students about the focus of the training positively affected training: The exposure duration needed for children informed about the focus of the training decreased more than for children who were not informed. This study suggests that neither of the two interventions is superior to the other in general. Rather, the improvement of general reading speed in a transparent orthography is closely related to both the children’s initial reading level and the type of words they practice with: common and familiar words when training their successes and uncommon and less familiar words with training their failures.29 p

Risk of complications and long-term functional alterations after local excision of rectal tumors with transanal endoscopic microsurgery (TEM)

Transanal endoscopic microsurgery (TEM) is a consolidated technique for the excision of rectal tumors. However, many aspects relating to its morbidity, risk of functional alterations, and therapeutic outcomes are still unclear. The aim of this study was to assess the rate of morbidity and fecal incontinence after TEM, and to identify associated risk factors

Quality of life after surgery for rectal cancer

Patients' health-related quality of life (HRQoL) is now considered a relevant clinical outcome. This study systematically reviewed articles published in the last 5 years, focusing on the impact of rectal cancer treatment on patients' HRQoL. Of the 477 articles retrieved, 56 met the inclusion criteria. The most frequently reported comparisons were between surgical procedures (21 articles), especially between sphincter-preserving and non-sphincter preserving surgery or between stoma and stoma-free patients (13 articles), and between multimodality therapies (11 articles). Additionally, twelve articles compared patients' and healthy controls' HRQoL as primary or secondary aim. The majority of the studies were observational (84 %), controlled (66 %), cross-sectional (54 %), prospective (100 %), with a sample of more than 100 patients (59 %), and with more than 60 % of patients treated with neoadjuvant therapy (50 %). The most frequently used instruments were the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30), its colorectal cancer specific module QLQ-CR38, and the Medical Outcomes Study Short-Form 36 items questionnaire. Findings from the included articles are summarised and commented, with a special focus on the comparison between surgical treatments, between irradiated and not-irradiated patients, and between patients and the general population