Biomedical subjects

Mark D Vincent

Publications and source records attributed to Mark D Vincent.

4 recordsLinked to original sources

PubMed2003

Continued cigarette smoking by patients receiving concurrent chemoradiotherapy for limited-stage small-cell lung cancer is associated with decreased survival.

PURPOSE: To determine the impact of continued smoking by patients receiving chemotherapy (CHT) and radiotherapy (RT) for limited-stage small-cell lung cancer (LSCLC) on toxicity and survival. PATIENTS AND METHODS: A retrospective review was carried out on 215 patients with LSCLC treated between 1989 and 1999. Treatment consisted of six cycles of alternating cyclophosphamide, doxorubicin, vincristine and etoposide, cisplatin (EP). Thoracic RT was concurrent with EP (cycle 2 or 3) only. Patients were known smokers, with their smoking status recorded at the start of chemoradiotherapy (CHT/RT). RT interruption during concurrent CHT/RT was used as the marker for treatment toxicity. RESULTS: Of 215 patients, smoking status was recorded for 186 patients (86.5%), with 79 (42%) continuing to smoke and 107 (58%) abstaining during CHT/RT. RT interruptions were recorded in 38 patients (20.5%), with a median duration of 5 days (range, 1 to 18 days). Median survival for former smokers was greater than for continuing smokers (18 v 13.6 months), with 5-year actuarial overall survival of 8.9% versus 4%, respectively (log-rank P =.0017). Proportion of noncancer deaths was comparable between the two cohorts. Continuing smokers did not have a greater incidence of toxicity-related treatment breaks (P =.49), but those who continued to smoke and also experienced a treatment break had the poorest overall survival (median, 13.4 months; log-rank P =.0014). CONCLUSION: LSCLC patients who continue to smoke during CHT/RT have poorer survival rates than those who do not. Smoking did not have an impact on the rate of treatment interruptions attributed to toxicity.

Actuarial Analysis↗

PubMed2003

A "combination oligonucleotide" antisense strategy to downregulate thymidylate synthase and decrease tumor cell growth and drug resistance.

Thymidylate synthase (TS) catalyzes de novo production of thymidylate for DNA synthesis and cell proliferation. As such, TS has been a target of antitumor chemotherapy for many years. Our laboratory has identified several antisense oligodeoxynucleotides (ODNs) that downregulate TS mRNA and protein, inhibit cell proliferation, and sensitize cells to TS-directed chemotherapeutic drugs. Based on our observation that targeting distinct regions of the TS mRNA with a variety of antisense molecules resulted in differential effects on TS mRNA levels, it was hypothesized that use of multiple ODNs targeting distinct noncontiguous regions would result in synergistic or antagonistic interactions. In this study, we report that some combinations of TS antisense ODNs were more effective at reducing TS mRNA abundance and inhibiting cell proliferation than the individual ODNs used alone. However, in contrast to the effects on cell proliferation, the enhanced sensitivity to anti-TS chemotherapeutic drugs (i.e., raltitrexed and 5-fluorodeoxyuridine) that is achieved by treatment with individual ODNs was not further augmented by combined ODN treatment. This suggests that ODNs targeting TS mRNA inhibit an alternative function of TS mRNA or protein, distinct from thymidylate production. The results are evidence that the novel use of multiple antisense ODNs that target different regions of the same mRNA represents a general strategy to improve antisense effectiveness.

Antineoplastic Agents↗

PubMed2003

Primary chemoradiation as definitive treatment for unresectable cancer of the trachea.

A 64-year-old man was diagnosed with unresectable cancer of the trachea. He was treated definitively with a novel chemoradiation regimen. Cisplatin-based chemotherapy (ChT) was given for two cycles as induction, followed by concurrent administration of this ChT with external beam radiotherapy (RT) (total dose 60 Gy). An unexpected partial tumour response was noted after the induction of ChT alone. Six weeks after finishing ChT/RT, complete response of the lesion was noted on computed tomography imaging. Two years later, the patient was free of disease. Primary chemoradiation appears to be effective in managing locally advanced tracheal cancer.

Anticoagulants↗

PubMed2002

Multicenter phase III study of uracil/tegafur and oral leucovorin versus fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer.

PURPOSE: This phase III study was designed to demonstrate equivalence in survival of oral uracil/tegafur (UFT) and oral leucovorin (LV) to conventional intravenous (IV) fluorouracil (5-FU) and LV in previously untreated metastatic colorectal carcinoma. Safety was also compared. PATIENTS AND METHODS: Eight hundred sixteen patients were randomized to receive either UFT (300 mg/m(2)/d) and LV (75 or 90 mg/d) for 28 days every 35 days or IV bolus 5-FU (425 mg/m(2)/d) and LV (20 mg/m(2)/d) for 5 days every 28 days. RESULTS: UFT/LV produced survival comparable to the IV 5-FU/LV regimen. Median survival was 12.4 months (95% confidence interval [CI], 11.2 to 13.6 months) with UFT/LV and 13.4 months (95% CI, 11.6 to 15.4 months) with 5-FU/LV (P =.630). The hazard ratio for survival was 0.964 (95.6% CI, 0.826 to 1.125), supporting equivalent survival. The overall response rate did not differ between treatment arms (UFT/LV, 11.7%; 5-FU/LV, 14.5%; P =.232). Median time to progression favored 5-FU/LV (UFT/LV, 3.5 months; 5-FU/LV, 3.8 months; P =.011), but tumor assessment schedules differed between arms. UFT/LV significantly improved safety compared with 5-FU/LV. Diarrhea, nausea and vomiting, and stomatitis and mucositis were significantly less frequent with UFT/LV, as was myelosuppression. Patients treated with UFT/LV had fewer episodes of febrile neutropenia (P <.001) and documented infections (P <.05). Increased bilirubin, without other liver function abnormalities, was observed more often with UFT/LV (P <.001). Concomitant medications were more frequent with 5-FU/LV, including use of antibiotics, growth factors, and antiemetics. CONCLUSION: UFT/LV provided a safer, more convenient oral alternative to a standard bolus IV 5-FU/LV regimen for metastatic colorectal cancer while producing equivalent survival.

Administration, Oral↗