Crop Protection Discovery: Is Being the First Best?

Current crop protection chemicals span an array of chemistry classes and modes of action. Typically, within each chemistry class, there are multiple chemically distinct active ingredients competing with each other for market position. In this competition, the first product to market in a new class or mode of action may or may not have an advantage depending upon a number of parameters, including relative efficacy against the target pests, pest resistance, regulatory pressures, synthetic complexity, and marketing effectiveness. The number of companies involved in the discovery of new crop protection compounds has been declining, and patenting strategies have become more sophisticated, making it more challenging to break into an existing area of chemistry. One result is new classes of chemistry tend to be smaller, making first to market more beneficial than in the past. Additionally, the first into a market with a new class of chemistry has the opportunity to set positioning and expectations.

Lead generation in crop protection research: a portfolio approach to agrochemical discovery.

The need for increased food and feed supply to support future global demand with the added challenges of resistance pressure and an evolving regulatory environment necessitates the discovery of new crop protection agents for growers of today and tomorrow. Lead generation is the critical 'engine' for maintaining a robust pipeline of new high-value products. A wide variety of approaches exist for the generation of new leads, many of which have demonstrated success. Each approach features some degree of merit or benefit while also having some inherent drawback or level of risk. While risk for any single approach can be mitigated in a variety of different ways depending on the approach, long-term viability of a successful lead generation program merits utilization of a portfolio of different approaches and methodologies for the generation of new leads. © 2016 Society of Chemical Industry.

A phase I-II trial of weekly topotecan in the treatment of recurrent cervical carcinoma.

In recent phase III studies, intravenous topotecan (0.75 mg/m(2)) plus cisplatin demonstrated significant progression-free and overall-survival benefits in patients with advanced and recurrent cervical cancer. However, the regimen demonstrated clinically significant myelotoxicity. The current study was undertaken to examine the safety, tolerability, and efficacy of weekly bolus topotecan in patients with advanced or metastatic disease. All patients had biopsy-confirmed disease not amenable to radiation treatment or surgery. Lesions were measurable bidimensionally, and patients had adequate hematologic, hepatic, and renal function. Patients received 3.5 mg/m(2) topotecan intravenously on days 1, 8, and 15 of a 28-day cycle. If no grade 3 or 4 hematologic toxicities occurred, the dose was escalated to 4 mg/m(2) in the third cycle. Safety, tolerability, and response rates were the primary endpoints. In addition to weekly hematologic assessments, Eastern Cooperative Oncology Group status was evaluated monthly, and tumor response was evaluated every alternate cycle. Twenty patients were enrolled and evaluated for toxicity and tumor response. Grade 3 toxicity occurred in 8/48 (17%) treatment cycles. There was only one drug-related adverse toxicity that required a dose reduction. Grade 1/2 hematologic toxicities were rare and only accounted for 1 (2%) of the dose delays (1 week). Two (10%) patients achieved stable disease for a mean of 5.3 months. The weekly bolus topotecan regimen used in the current study was well tolerated. Future phase II studies of weekly bolus topotecan in combination with cisplatin in this patient population may be warranted.

Confirmatory chest radiographs after central line placement: are they warranted?

OBJECTIVES: This study was designed to determine the ability of physicians to predict complications associated with the placement of central venous access devices and to decide whether a confirmatory chest radiograph is warranted after placement. METHODS: Patients receiving central venous access on an inpatient and outpatient gynecologic oncology service were studied. Data were collected regarding patient demographics, patient history, procedural details of the placement, and the type of catheter used. The physician then predicted which patients had a reasonable potential for placement complications. All of the patients then underwent radiography, which was then compared with the original prediction. RESULTS: Ninety-eight patients who had central venous access devices placed were included in the study. Eighty of the 81 central lines thought by the practitioner to have been placed without incident caused no significant complications; one individual in this group had a minor pneumothorax. Two of 17 patients predicted to have complications were noted to have a pneumothorax that required hospitalization. No patients in the low-risk group were hospitalized for a placement complication, whereas two hospitalizations occurred in the high-risk group. CONCLUSION: Confirmatory chest radiographs may potentially be omitted in certain cases after line placement when experienced clinicians use good technique, good clinical judgment, and discrimination.

Effect of topotecan infusion duration on hematologic toxicity in recurrent ovarian carcinoma.

In an open-label, multicenter, nonrandomized, counterbalanced study, we investigated the tolerability and antitumor profile of a 10-min infusion duration of topotecan. A total of 12 patients with evaluable recurrent ovarian cancer were enrolled into the study and treated with 1.5 mg/m2/d topotecan for 5 d of a 21-d course by either a 10-, 30-, or 120-min intravenous infusion. Patients were evaluated for tolerability and tumor response. The primary toxicity associated with topotecan was noncumulative myelosuppression. All 12 patients experienced grade 3/4 neutropenia. Grade 3/4 thrombocytopenia, leukopenia, and anemia were reported in five (42%), two (17%), and two (17%) patients, respectively. Likewise, the majority of courses were associated with hematologic toxicity, with grade 3/4 neutropenia, thrombocytopenia, leukopenia, and anemia reported in 97%, 19%, 6%, and 6% of courses, respectively. The infusion duration had little impact on the myelotoxicity profile of topotecan. The mean nadir levels for all hematologic parameters were similar for all infusion durations, and myelosuppression was reversible and returned to near-preinfusion levels prior to administering the subsequent course, irrespective of infusion duration. A complete response was obtained by three (25%) patients, and five (42%) patients achieved stable disease; therefore, 67% of patients obtained clinical benefit. The results of this study demonstrate that topotecan administered over a 10-min interval has a comparable tolerability and safety profile compared with a 30-min infusion. A 10-min infusion may result in greater patient convenience and a reduction in the consumption of healthcare resources.