Phase II trial of trimelamol in refractory ovarian cancer

Trimelamol is an analogue of hexamethymelamine which exhibited activity against refractory ovarian cancer in phase I clinical trial. The dose limiting toxicity was leukopenia. In a phase II study, 42 patients with recurrent, or platinum-complex resistant, advanced ovarian cancer were treated using the dose schedule 800 mg m-2 i.v. daily for 3 days. There were one complete, three partial and five minor responses, objective response rate: 9.5%. The main toxicity observed was nausea and vomiting, myelosuppression was minor. The role of Trimelamol in the treatment of ovarian cancer remains to be defined, but its activity is limited in refractory disease

A randomised study of carboplatin vs sequential ifosfamide/carboplatin for patients with FIGO stage III epithelial ovarian carcinoma

In a study designed to compare response rates of patients with stage III epithelial ovarian carcinoma to ifosfamide and carboplatin, 152 patients were randomised to receive either sequential therapy with three cycles of ifosfamide followed by three cycles of carboplatin, or to six cycles of single agent carboplatin. Ifosfamide was given every 3 weeks in a dose of 5 gm m-2 as a 24 h infusion with mesna, 1 gm m-2 by i.v. bolus prior to ifosfamide, 3 gm m-2 with ifosfamide, and 1 gm m-2 as an 8 h infusion after ifosfamide. Carboplatin was given in a dose of 400 mg m-2 by short i.v. infusion every 4 weeks. Sixty-eight evaluable patients were randomised to sequential ifosfamide/carboplatin, and 67 to single agent carboplatin. Median follow-up is 36 months (range 5.5-82.3). After three cycles of treatment two patients in the ifosfamide/carboplatin arm achieved complete remission (CR), and 12 partial remission (PR) for an overall response rate of 29%, whereas in the carboplatin arm ten patients achieved CR, and 23 PR, for an overall response rate of 63% (P = 0.0008). Seven of 15 patients with progressive disease, and nine of 20 patients with stable disease at the initial response evaluation, following three cycles of ifosfamide, subsequently responded to carboplatin therapy so that the final response rate to the complete regimen was 65% for the ifosfamide/carboplatin arm, compared to 71% for the carboplatin arm (NS). For the ifosfamide/carboplatin arm, median recurrence free survival and overall survival were 14.1 months and 18.7 months. Corresponding figures for the carboplatin arm were 14.5 months and 21.5 months (NS). Both treatments were generally well tolerated. However 47% of patients in the ifosfamide/carboplatin arm developed alopecia sufficient to require a wig, compared to only 2% in the carboplatin arm. Ifosfamide is clearly less effective, and more toxic than carboplatin. Ifosfamide failures can however be effectively salvaged by subsequent carboplatin treatment. Ifosfamide cannot be recommended for single agent therapy in ovarian carcinoma, however the combination of carboplatin plus ifosfamide might be a suitable treatment to be tested in a future randomised study against carboplatin alone

A phase I and pharmacokinetic study of indisulam in combination with carboplatin

Indisulam (E7070) is an anticancer agent that is currently being evaluated in phase II clinical studies. A significant reduction in glutathione synthetase and glutathione reductase transcripts by indisulam provided a molecular basis for its combination with platinum agents. Indisulam demonstrated high anti-tumour activity in various preclinical cancer models. The objectives of this study were (1) to determine the recommended dose of indisulam in combination with carboplatin in patients with solid tumours and (2) to evaluate the pharmacokinetics of the combination. Patients with solid tumours were treated with indisulam in combination with carboplatin. Indisulam (350, 500, or 600 mg m−2) was given as a 1-hour intravenous infusion on day 1 and carboplatin (5 or 6 mg min ml−1) as an intravenous infusion over 30 min on day 2 of a three-weekly cycle. Sixteen patients received study treatment and were eligible. Thrombocytopenia was the major dose limiting toxicity followed by neutropenia. Both drugs contributed to the myelosuppressive effect of the combination. Indisulam 500 mg m−2 in combination with carboplatin 6 mg min ml−1 was identified not to cause dose limiting toxicity, but a delay of re-treatment by 1 week was required regularly to allow recovery from myelosuppression. The recommended dose and schedule for an envisaged phase II study in patients with non-small cell lung cancer is indisulam 500 mg m−2 in combination with carboplatin 6 mg min ml−1 repeated four-weekly. Patients who do not experience severe thrombocytopenia at cycle 1 will be permitted to receive an escalated dose of indisulam of 600 mg m−2 from cycle 2 onwards

First-line treatment for advanced ovarian cancer: paclitaxel, platinum and the evidence

Four large randomised trials of paclitaxel in combination with platinum against a platinum-based control treatment have now been published in full, representing around 88% (3588 out of 4057) of patients randomised into the eight known trials of this question. There is substantial heterogeneity in the results of these four trials. Four main explanations for this heterogeneity have been proposed: differences in the extent and timing of ‘crossover’ to taxanes in the control groups; differences in the types of patient included; differences in the effectiveness of the research regimens used; differences in the effectiveness of the control regimens used. In this study we examine whether any of these explanations is consistent with the pattern of results seen in these trials. Each explanation suggests that a particular characteristic of each trial was responsible for the results observed. For each explanation the trials were split into groups according to that characteristic, in order to partition the total heterogeneity into that seen ‘within’ and ‘between’ groups of trials. If a particular explanation was consistent with the pattern of results, we would expect to see relatively little heterogeneity within each group of trial results viewed in this way, with most of the heterogeneity being between groups which are dissimilar with respect to the key characteristic. Heterogeneity ‘within’ and ‘between’ groups was formally compared using the F-ratio. If any explanation appeared to be consistent with the results of the trials, it was considered whether the explanation was also consistent with other evidence available about these regimens. Only one explanation appeared to be consistent with the pattern of results seen in these trials, and that was differences in effectiveness of the control arms used in these trials. This suggests that the very positive results in favour of paclitaxel/cisplatin seen in two of the trials may have been due to the use of a suboptimal control arm. There is no direct evidence about the relative effectiveness of the control arms used in these trials, but indirect evidence is consistent with the conclusion that the cyclophosphamide/cisplatin regimen used in two of the trials may be less effective than the control regimens used in the other trials. Specific concerns about the choice of a cyclophosphamide/cisplatin control arm in the first of these trials to report were raised before the results of the other trials were known, i.e. before any heterogeneity had been observed. Further investigation of this question would be useful. In the meantime, given all of the randomised evidence on the efficacy and toxicity associated with the regimens used in these trials, we conclude that single agent carboplatin is a safe and effective first-line treatment for women with advanced ovarian cancer

Skeletal Plasmacytoma: Progression of disease and impact of local treatment; an analysis of SEER database

<p>Abstract</p> <p>Background</p> <p>Previous reports suggest an as yet unidentifiable subset of patients with plasmacytoma will progress to myeloma. The current study sought to establish the risk of developing myeloma and determine the prognostic factors affecting the progression of disease.</p> <p>Methods</p> <p>Patients with plasmacytoma diagnosed between 1973 and 2005 were identified in the SEER database(1164 patients). Patient demographics and clinical characteristics, treatment(s), cause of death, and survival were extracted. Kaplan-Meier, log-rank, and Cox regression were used to analyze prognostic factors.</p> <p>Results</p> <p>The five year survival among patients initially diagnosed with plasmacytoma that later progressed to multiple myeloma and those initially diagnosed with multiple myeloma were almost identical (25% and 23%; respectively). Five year survival for patients with plasmacytoma that did not progress to multiple myeloma was significantly better (72%). Age > 60 years was the only factor that correlated with progression of disease (p = 0.027).</p> <p>Discussion</p> <p>Plasmacytoma consists of two cohorts of patients with different overall survival; those patients that do not progress to systemic disease and those that develop myeloma. Age > 60 years is associated with disease progression. Identifying patients with systemic disease early in the treatment will permit aggressive and novel treatment strategies to be implemented.</p

Poliomyelitis surveillance report number 18, May 20, 1955

Dr. Edwin Lennette, Virus Laboratory, California Department of Public Health, reports isolation of type 1 virus from the stool of case PSU No. Cal-21. He also reports isolation of type 1 virus from the stool of a third \uc2\ub0th contact of non-paralytic case PSU No. Cal-14. Isolations from 2 other contacts of this case were previously reported.Dr. Werner Henle, Children\ue2\u20ac\u2122s Hospital, Philadelphia, reports isolation of type 1 poliomyelitis virus from Case PSU No. Pa-2. This is the first isolation from a case receiving Wyeth Vaccine. This case had first paralysis at the same site as inoculation.One new case was accepted today from West Virginia. This seven-year-old female developed bulbar signs 26 days after inoculation with Lilly Vaccine. Vaccinated cases total 79 at 12:00 noon 5-20-55 (Table l)