Feasibility of preoperative chemoradiation in rectal cancer patients aged 70 and older.

In the present study, we report results of 28 rectal cancer patients, aged 70 years and older, treated with preoperative radiotherapy and 5FU concomitant chemotherapy. Twenty-eight out of 136 patients treated in our Department between 1997 and 2004 aged > or = 70 years, mean 73 (range 70-81); 3 T2, 18 T3, 7 T4; 15 N0, 5N1, 8 N2; Radiotherapy (5040 cGy, 28 fractions) was delivered combined with 5FU - based concomitant chemotherapy. Compliance to chemoradiotherapy was excellent. Major acute toxicity (> or = G3) evaluation showed haematological Grade 3 only in 2 patients. No severe acute Gastrointestinal toxicity was observed. All patients underwent surgery without severe perioperative complications. Complete pathological response pT0 was found in 3 patients (11%). Overall T downstaging occurred in 61% of the cases. Mean follow up was 34 months (range 4- 84). Kaplan Meier Overall Survival and Disease Free Survival at 5 years were 74% (95% CI 54 -95) and 65% (95% CI 38-93), respectively. Only 1 patient showed G3 diarrhea according to CTCAE that interfered with his Quality of Life and required hospitalization. In conclusion, concomitant radiochemotherapy 5FU based is safe in rectal cancer patients aged > or = 70 with a good tumour downstaging (61% of patients) and excellent feasibility. No treatment related death was observed.

Low-dose vincristine-associated bilateral vocal cord paralysis.

BACKGROUND: Vincristine-associated peripheral neuropathy is a well-described entity. We describe a case of vincristine-induced vocal cord paralysis, which is a rare complication of this drug. We report herein the second case of bilateral vocal cord paralysis in a patient receiving conventional doses of vincristine. OBJECTIVE: To present a case report of vincristine-associated vocal cord paralysis and to review the relevant English language literature on this subject. DESIGN: Report and review of the literature. SETTING: Outpatient community cancer center. PATIENT: A 58-year-old female with a diffuse large cell lymphoma stage IV receiving cyclophosphamide, doxorubicin, vincristine, and prednisone. RESULTS: Bilateral vocal cord paralysis occurred in this patient receiving vincristine as part of her chemotherapy regimen. In addition to this case there have been a total of 25 prior reports, which are reviewed in the text. CONCLUSION: The incidence of bilateral vocal cord paralysis in patients receiving vincristine on the usual low-dose schedule is low. Prompt withdrawal of the offending agent results in prompt recovery without untoward long-lasting sequela.

Randomized phase II study of the neurokinin 1 receptor antagonist CJ-11,974 in the control of cisplatin-induced emesis.

PURPOSE: To determine the efficacy and safety of the neurokinin type 1 receptor antagonist CJ-11,974 for the control of high-dose cisplatin-induced emesis. PATIENTS AND METHODS: A double-blind, randomized, phase II design with a group sequential stopping rule was used in this study. Sixty-one patients with cancer who were receiving cisplatin at a dose of at least 100 mg/m2 for the first time were enrolled. All patients received granisetron 10 microg/kg and dexamethasone 20 mg intravenously 30 minutes before they were given cisplatin. Patients were randomly assigned to two groups: group 1 received CJ-11,974 100 mg, and group 2 received placebo orally 30 minutes before and 12 hours after cisplatin and then twice daily on days 2 through 5 after cisplatin. The primary end point was the percentage of patients who developed delayed emesis (emesis on the second to fifth days after cisplatin). RESULTS: Thirty patients were enrolled in group 1, and 31 patients were enrolled in group 2. Fifty-eight patients were assessable for efficacy. Complete control of emesis (expressed as the percentage of patients who had no emesis) was as follows: day 1, 85.7% (group 1) and 66.7% (group 2) (P = .090); days 2 through 5, 67.8% (group 1) and 36.6% (group 2) (P = .0425, adjusted); days 1 through 5, 64.3% (group 1) and 30% (group 2) (P = .009). Patients in group 1 experienced significantly less nausea than patients in group 2 on day 1 (P = .024). Treatment was well tolerated in both groups. CONCLUSION: We conclude from this exploratory phase II trial that CJ-11,974 is superior to placebo in controlling cisplatin-induced delayed emesis and may provide additive benefit in acute emesis and nausea control when combined with a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. Additional larger trials are indicated to confirm the clinical value of CJ-11,974.

A phase II study of mitomycin C, vindesine and cisplatin combined with alpha interferon in advanced non-small cell lung cancer.

AIMS AND BACKGROUND: MVP chemotherapy (mitomycin C, vindesine or vinblastine, cisplatin) is one of the most commonly used regimens for advanced non-small cell lung cancer (NSLCLC). Experimental data suggest a synergistic cytotoxic activity of alpha-interferon (alpha-IFN) when combined with cisplatin, mitomycin C and vinca alkaloids. In an effort to improve MVP chemotherapy activity, we have combined this regimen with alpha-IFN. PATIENTS AND METHODS: Thirty-five patients with advanced NSCLC (19 stage IV) were treated with the MVP regimen (mitomycin C, 8 mg/m2; vindesine, 3 mg/m2, cisplatin, 75 mg/m2, all on day 1) plus alpha-2a-IFN, 3x10(6) U from day 1 to 7. The cycles were repeated every 28 days. RESULTS: There were no complete responses and 18 partial responses, for an overall response rate of 51%. Median time to treatment failure was 6 months (range, 1-18), and the median survival was 9.5 months (range, 1-32). WHO grade 3 toxicity was recorded in up to 8% of patients, flu-like syndrome was a common complaint; one toxic death occurred. CONCLUSIONS: The combination yielded a level of response comparable to that of other cisplatin-based regimens. Larger randomized trials are needed to assess the role of alpha-IFN combined with chemotherapy in advanced NSCLC.

Dacarbazine, cisplatin and carmustine, with or without tamoxifen, for metastatic melanoma: 5-year follow-up.

Metastatic melanoma has a grim prognosis. Response rates and survival of patients treated with combination chemotherapy are not superior to single-agent chemotherapy. This study seeks to evaluate the objective response rate and survival of patients with metastatic melanoma treated with multiagent chemotherapy, with or without tamoxifen. Forty-two patients with metastatic melanoma were treated from March 1982 to February 1988 with dacarbazine, cisplatin and carmustine, with or without tamoxifen. An overall objective response rate of 43% was seen (complete response rate 17%; partial response rate, 26%). The response rate was 54% for patients treated with tamoxifen and 25% for patients treated without tamoxifen, but the results did not achieve statistical significance. Median overall survival was 412 days, and was significantly longer in the tamoxifen-treated group. Combination chemotherapy as described in this study is well-tolerated. The observation that tamoxifen appears to impact on survival should be interpreted with great caution due to the deficiencies in the design of the trial and small patient numbers. A randomized trial of this regimen vs single-agent chemotherapy is indicated and is currently being conducted.

Mitomycin C, 5fluorouracil and folinic acid in combination with alpha 2b interferon for advanced colorectal cancer.

AIMS AND BACKGROUND: This study was conducted to investigate the activity and toxicity of 5fluorouracil folinic acid+mitomycin C combined with alpha 2b interferon in advanced colorectal cancer based upon recent studies suggesting a possible biochemical modulation of 5fluorouracil by interferon. PATIENTS AND METHODS: Between June 1990 and April 1991 25 previously untreated patients with advanced colorectal carcinoma were treated with mitomycin C 10 mg/m2 iv bolus on day 1, 5fluorouracil 375 mg/m2 on days 1 to 4 and folinic acid 200 mg/m2 on days 1 to 4 every 4 weeks, combined with alpha 2b interferon 3 million U day continuously. RESPONSE: Of the 25 patients entered into the study, 20 were evaluable for response as 5 patients withdrew due to toxicity (grade 3-4 thrombocytopenia in 4 cases and fatigue in 1). No complete response was recorded, 6 patients had partial remission (30%; 95% confidence interval, 10% to 50%), 4 experienced no change and 10 showed progressive disease. The toxicity of this regimen was significant, particularly myelosuppression. CONCLUSIONS: This combination showed a significant toxicity and low response rate compared with other 5fluorouracil based regimens in advanced colorectal cancer.

Atherosclerosis and coronary bypass surgery in hereditary factor VII deficiency.

A 66-year-old man with homozygous deficiency of factor VII (less activity than 4 percent of normal) had a minimal hemorrhagic tendency and severe coronary atherosclerosis, and underwent aortocoronary saphenous vein bypass surgery. Although plasma factor VII coagulant activity and cross-reacting material were markedly reduced, comparable amounts of factor VII antigen were detected in peripheral blood mononuclear cells of both the patient and of a normal subject by Western blotting techniques. Accelerated coagulation was observed following brief exposure of the patient's phytohemagglutinin-stimulated peripheral blood mononuclear cells to low concentrations of ambient factor VII in vitro. Evidence indicates that factor VII plays a role in vivo in both hemostasis and atherogenesis and it might be assumed that factor VII deficiency would both predispose to excessive bleeding and forestall atherosclerosis. However, these observations suggest that factor VII-mediated thrombin generation may proceed by partitioning of small amounts of factor VII on tissue factor-expressing cells and that factor VII contained within monocytes may facilitate tissue factor-induced coagulation by these cells. These features may provide efficient coagulation activation despite a deficiency of the plasma coagulant protein. The current results may explain, at least in part, the minimal bleeding tendency, and also the occurrence of thrombosis and atherosclerosis in certain persons with factor VII deficiency.

Cisplatin and radiation therapy for locally advanced squamous cell carcinoma of the lung.

A pilot study was initiated to test the safety and efficacy of the simultaneous administration of high-dose cisplatin and irradiation in patients with locally advanced squamous cell carcinoma of the lung. Cisplatin was administered at 100 mg/m2 on Days 1 and 21 and was continued at 20 mg/m2 once a week to the completion of radiation therapy. Irradiation was begun on Day 22 and was administered 5 days a week for 6 weeks at a rate of 200 cGy per day to a total of 6000 cGy to the primary site, using a shrinking field technique. Of the 13 patients so treated, all but one showed objective evidence of tumor regression according to chest x-ray. Six patients are still alive from 12 to 37 months after the start of treatment, including four who are asymptomatic and without apparent tumor and two with persistent local disease. Of the seven patients who died, four had metastatic disease (including one with local recurrence as well), one (who had been resistant to therapy) had persistent local disease, and two died too early to allow comment on efficacy (although autopsy in one case showed no evidence of locoregional tumor). This program is both active and tolerable, and deserves further study.