The chickpea root rot complex in Saskatchewan, Canada- detection of emerging pathogens and their relative pathogenicity.

Chickpea fields in Saskatchewan, one of the three Canadian prairie provinces, have suffered from major health issues since 2019, but no definitive cause has been determined. Field surveys were conducted in Saskatchewan in 2020 and 2021 in order to develop a better understanding of root rot pathogens associated with chickpea. Root samples were analyzed for the presence of 11 potential chickpea root rot pathogens using end-point PCR. Fusarium redolens, F. solani and F. avenaceum were the most prevalent pathogen species detected in both survey years. The cause of Fusarium wilt in chickpea, F. oxysporum f. sp. ciceris, was not detected in either year, nor were Phytophthora spp. and Verticillium albo-atrum. Berkeleyomyces sp. was detected in one field in each year, and Verticillium dahliae was detected in several fields sampled in 2021. These two pathogens have not been reported previously on chickpea in Saskatchewan. The prevalence of Fusarium species obtained from 2021 root isolations was similar to that determined by molecular tests, with frequent isolation of F. redolens, F. oxysporum, F. avenaceum and F. solani. A series of indoor pathogenicity testing compared root disease severity caused by a selection of 16 isolates of six Fusarium species and single isolates of V. dahliae, Berkeleyomyces sp. and Macrophomina phaseolina. Results showed that select isolates of F. avenaceum were the most aggressive of the Fusarium isolates on chickpea. Despite relatively low inoculum density, a highly aggressive isolate of F. avenaceum caused severe stunting and more root rot symptoms than single isolates of V. dahliae, Berkeleyomyces sp. and M. phaseolina under the test conditions.

A phase II study of gefitinib, 5-fluorouracil, leucovorin, and oxaliplatin in previously untreated patients with metastatic colorectal cancer.

PURPOSE: We investigated the gefitinib, 5-fluorouracil (5-FU), leucovorin and oxaliplatin (IFOX) regimen as first-line therapy in patients with metastatic colorectal cancer. EXPERIMENTAL DESIGN: Eligible patients had stage IV colorectal adenocarcinoma, and had not received prior chemotherapy for metastatic disease. Each cycle consisted of 14 days. Cycle 1 consisted of oxaliplatin, leucovorin, and 5-FU (FOLFOX-4). All subsequent cycles consisted of FOLFOX-4 with gefitinib at 500 mg orally daily throughout the 14-day cycle. RESULTS: Forty-five patients were enrolled and were assessable for toxicity. Forty-three patients were assessable for response. Thirty-one of the 43 patients (72%) had either a complete or partial response by the Response Evaluation Criteria in Solid Tumors. Median overall survival was 20.5 months. Median time to progression was 9.3 months. Commonly encountered grade 3 or 4 toxicities included diarrhea in 67% of patients and neutropenia in 60%. Grade 2 acneiform skin rash typical of gefitinib occurred in 60% of patients. CONCLUSIONS: IFOX is an active first-line regimen in patients with metastatic colorectal adenocarcinoma, showing higher response rates but also increased toxicities compared with FOLFOX-4 alone in a similar patient population.

Glomerella truncata sp. nov., the teleomorph of Colletotrichum truncatum.

Anthracnose of lentil, caused by Colletotrichum truncatum is a serious threat to lentil (Lens culinaris) grown in western Canada. The teleomorph stage of this pathogen was induced to form under laboratory conditions. Random pairing of single conidium isolates enabled the identification of fertile isolates. The individual isolates of this fertile pair were crossed with 14 other isolates, and all isolates were also incubated alone. Self-sterility was observed for all 16 isolates tested. Three isolates did not produce perithecia with either tester isolate, and none of the isolates tested produced perithecia with both tester isolates. Perithecia were brown-black, superficial, solitary or in small groups, obpyriform to ovate or ampulliform, 200-520 x 110-320 microm (mean: 350 x 200 microm). Asci were cylindrical, narrowing slightly at the apex, unitunicate, evanescent, 53-142 x 5-14 microm (mean: 90 x 8 microm), and contained eight ascospores. Ascospores were hyaline, aseptate, oblong, 12-20 x 5-8 microm (mean: 15.7-6.7 microm). The characteristics agree with those described for the genus Glomerella, and the species was named G. truncata sp. nov. The morphology of the new species is compared with that of other species in the genus, and future research on G. truncata is described.

Phase I study of 131I-chimeric(ch) TNT-1/B monoclonal antibody for the treatment of advanced colon cancer.

PURPOSE: The primary aim of this study was to evaluate the biodistribution and toxicity of 131I-chimeric(ch) TNT-1/B monoclonal antibody (MAB), which binds to intracellular antigens of necrotic regions within tumors, in patients with advanced colon or colorectal cancer. The rationale for targeting areas of tumor necrosis is the observation that necrotic lesions are more abundant in cancer lesions than in surrounding tissues. PATIENTS AND METHODS: Cohorts of patients with advanced colon or colorectal cancer were administered a one-time 30-60-minute intravenous (i.v.) infusion of 131I-chTNT-1/B at doses ranging from 12.95 to 66.23 MBq/kg (0.35-1.79 mCi/kg). RESULTS: The dose-limiting toxicity, experienced at 66.23 MBq/kg (1.79 mCi/kg) 131I-chTNT-1/B MAB, was myelosuppression. Two (2) patients at the 66.23-MBq/kg (1.79 mCi/kg) dose level had both grade 3 thrombocytopenia and grade 3 neutropenia that persisted for at least 2 weeks but were reversible. The maximum tolerated dose was 58.09 MBq/kg (1.57 mCi/kg) 131I-chTNT-1/B MAB. Of the 21 patients, one developed a moderate human antichimeric antibody (HACA) response and 6 developed low HACA responses. CONCLUSIONS: The infusion of 131I-chTNT-1/B MAB was well tolerated, without significant nonhematological toxicity. No patient obtained a complete or partial response, based on tumor cross-product response criteria. Tumor localization was seen in patients with dose levels at, and exceeding, 50.23 MBq/kg (1.36 mCi/kg) 131I-chTNT-1/B MAB.

Phase I study of gefitinib, oxaliplatin, 5-fluorouracil, and leucovorin (IFOX) in patients with advanced solid malignancies.

PURPOSE: Aphase 1 study of gefitinib in combination with oxaliplatin, 5-fluorouracil and leucovorin (IFOX)was conducted to evaluate the safety and feasibility of this regimen. PATIENTS AND METHODS: Patients with advanced solid malignancies were treated with escalating doses of gefitinib (250 mg or 500 mg once daily) in combination with FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin). The initial dose of oxaliplatin was 70 mg/m2 with sequential dose escalation to 85 mg/m2. RESULTS: Sixteen patients received a total of 138 14-day courses of daily gefitinib in combination with FOLFOX. Escalation of gefitinib from 250 mg/d to 500 mg/d with FOLFOX was well-tolerated. In addition, no severe toxicities precluded subsequent dose escalation of oxaliplatin from 70 mg/m2 to 85 mg/m2 at which no dose-limiting toxicity was seen. No further dose escalation was performed as this represented the oxaliplatin dose administered in the standard FOLFOX-4 regimen. The most predominant toxicity was diarrhea, which was well controlled with oral antidiarrheal agents. Four partial remissions occurred in patients with metastatic colorectal cancer. CONCLUSIONS: Gefitinib as a 500 mg daily continuous dose was well tolerated in combination with full doses of FOLFOX-4.

Phase II study of gefitinib, fluorouracil, leucovorin, and oxaliplatin therapy in previously treated patients with metastatic colorectal cancer.

PURPOSE: To investigate the gefitinib, fluorouracil (FU), leucovorin, and oxaliplatin regimen (IFOX) in previously treated patients with metastatic colorectal cancer. PATIENTS AND METHODS: Eligible patients had stage IV colorectal adenocarcinoma and had demonstrated progression or intolerance to a prior chemotherapy regimen not including oxaliplatin. Each cycle consisted of 14 days. Cycle 1 consisted of oxaliplatin 85 mg/m2 intravenously (IV) during 2 hours on day 1, hours 0 to 2; leucovorin 200 mg/m2 IV on days 1 and 2, hours 0 to 2; FU 400 mg/m2 IV push on days 1 and 2; and FU 600 mg/m2 IV on days 1 and 2, hours 2 to 24 (FOLFOX-4). All subsequent cycles consisted of FOLFOX-4 with gefitinib at 500 mg/d administered orally throughout the 14-day cycle. RESULTS: Twenty-seven patients were enrolled onto the study. The median number of prior chemotherapy regimens was two, and 74% of all patients received prior irinotecan. Nine of the 27 patients (33%) and six of the 20 patients (30%) who had prior FU and irinotecan had a partial response by Response Evaluation Criteria in Solid Tumors Group criteria. Median overall survival was 12.0 months. Median event-free survival was 5.4 months. Grade 3 to 4 toxicities included neutropenia (48%), diarrhea (48%), nausea (22%), and vomiting (15%). CONCLUSION: IFOX is an active regimen in patients with previously treated metastatic colorectal adenocarcinoma, demonstrating higher response rates than those reported with FOLFOX-4 alone in a similar patient population.

Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer.

PURPOSE: To determine the feasibility and toxicity of delivering stereotactic radiosurgery to patients with locally advanced pancreatic cancer. METHODS AND MATERIALS: Patients with Eastern Cooperative Oncology Group performance status < or=2 and locally advanced pancreatic cancer were enrolled on this Phase I dose escalation study. Patients received a single fraction of radiosurgery consisting of either 15 Gy, 20 Gy, or 25 Gy to the primary tumor. Acute gastrointestinal toxicity was scored according to the Radiation Therapy Oncology Group criteria. Response to treatment was determined by serial high-resolution computed tomography scanning. RESULTS: Fifteen patients were treated at 3 dose levels (3 patients received 15 Gy, 5 patients received 20 Gy, and 7 patients received 25 Gy). At these doses, no Grade 3 or higher acute gastrointestinal toxicity was observed. This trial was stopped before any dose-limiting toxicity was reached, because the clinical objective of local control was achieved in all 6 evaluable patients treated at 25 Gy. CONCLUSIONS: It is feasible to deliver stereotactic radiosurgery to patients with locally advanced pancreatic cancer. The recommended dose to achieve local control without significant acute gastrointestinal toxicity is 25 Gy.

Phase I and pharmacokinetic study of BMS-188797, a new taxane analog, administered on a weekly schedule in patients with advanced malignancies.

PURPOSE: The purpose of this study was to establish the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and preliminary activity of BMS-188797 administered weekly. EXPERIMENTAL DESIGN: Patients with advanced malignancies were treated with escalating doses of BMS-188797 on a weekly schedule as a 1-h i.v. infusion. Plasma sampling was performed to characterize the pharmacokinetics of BMS-188797. RESULTS: Eighteen patients with advanced malignancies were enrolled at three dose levels ranging from 35 to 65 mg/m(2). The number of patients evaluated at each dose level was as follows: 35 mg/m(2) (n = 3); 50 mg/m(2) (n = 9); and 65 mg/m(2) (n = 6). At 65 mg/m(2), three of six patients had a DLT (one had grade 4 neutropenia lasting >7 days, and two had grade 3 diarrhea). Expansion of the 50-mg/m(2) dose cohort to nine patients established this dose as the MTD, with one patient experiencing a DLT (grade 4 neutropenia with fever). Two partial responses were observed (lung cancer, 7+ months; ovarian cancer, 6+ months durations), as well as two minor responses (esophageal cancer, 5 months; ovarian cancer, 5 months). Both patients with partial responses had been clinically resistant to paclitaxel. Plasma pharmacokinetic mean values of maximum concentration (C(max)) and area under the curve (AUC(0-48)) increased in a dose-dependent manner within the range of doses used in this study, and in three of four patients, the DLTs correlated with AUC. CONCLUSIONS: The MTD and the recommended Phase II dose of weekly BMS-188797 is 50 mg/m(2). The drug demonstrates antitumor activity in taxane-refractory solid tumors and is now being evaluated in combination with carboplatin.

Phase II trial of preoperative 3D conformal radiotherapy, protracted venous infusion 5-fluorouracil, and weekly CPT-11, followed by surgery for ultrasound-staged T3 rectal cancer.

PURPOSE: CPT-11 sensitizes tumor cells to radiation and in combination therapy with 5-fluorouracil (5-FU) results in enhanced cytotoxicity to metastatic colorectal cancer. We report the results from a Phase II trial of preoperative radiotherapy (RT), CPT-11, and 5-FU for patients with ultrasound-staged T3 rectal cancer. METHODS AND MATERIALS: Between April 1999 and August 2001, 32 patients (21 men, 11 women; median age 52 years, range 40-74) with biopsy-proven adenocarcinoma of the rectum were enrolled in the study. All patients underwent endorectal ultrasonography for staging (uT3N0 = 19; uT3N1 = 13; uT2N1 = 1). RT was prescribed to the draining lymph nodes (45 Gy in 1.8-Gy daily fractions) and tumor (50.4 Gy in 1.8-Gy daily fractions). Patients also received concurrent CPT-11 (50 mg/m(2), Days 1, 8, 15, and 22) and 5-FU (200 mg/m(2) daily, 7 d/wk, Days 1-33). Surgical resection was performed 6-10 weeks after completing chemoradiotherapy. RESULTS: Acute toxicity was frequently observed, and 18 patients (56%) required either a chemotherapy dose reduction or RT interruption of >3 days. One patient withdrew because of diarrhea and abdominal cramping (Grade III) after 10 days of treatment. Although no Grade IV toxicity was observed, Grade III diarrhea (n = 9, 28%), mucositis (n = 7, 21%), rectal sores (n = 7, 21%), abdominal cramping (n = 3, 9%) were noted. Of the 32 patients who underwent surgery, 12 had a complete pathologic response. Of the 32 patients, the disease of 23 (71%) was downstaged. The average length of hospitalization was between 5 and 12 days, with 1 patient staying 33 days. All patients were followed for disease-free survival. CONCLUSION: Although associated with frequent acute toxicity, the regimen is associated with significant tumor "downstaging." Additional patients and longer follow-up are necessary to define the role of this regimen fully.