A prospective randomised trial to study the role of levamisole and interferon alfa in an adjuvant therapy with 5-FU for stage III colon cancer

The purpose of this trial was to examine the efficacy of the addition of levamisole (LEV) or interferon alfa (IFN) to an adjuvant chemotherapy with 5-fluorouracil (5-FU) in patients with stage III colon cancer. According to a 2 × 2 factorial study design, 598 patients were randomly assigned to one of four adjuvant treatment arms. Patients in arm one received 5-FU weekly for 1 year, patients in arm two 5-FU plus LEV, in arm three 5-FU plus IFN and patients in arm four 5-FU, LEV and IFN. The relative risk of relapse and the relative risk of death were significantly higher for patients treated with LEV compared with those without LEV treatment (HR 1.452, 95% CI 1.135–1.856, P=0.0028; HR 1.506, 95% CI 1.150–1.973, P=0.0027, respectively). No significant impact on survival was observed for therapy with IFN in the univariate analysis. The addition of LEV to adjuvant 5-FU significantly worsened the prognosis of patients with stage III colon cancer. Interferon alfa had no significant influence on survival when combined with adjuvant 5-FU, but increased the toxicity of therapy substantially

Revisiting perioperative chemotherapy: the critical importance of targeting residual cancer prior to wound healing

<p>Abstract</p> <p>Background</p> <p>Scientists and physicians have long noted similarities between the general behavior of a cancerous tumor and the physiological process of wound healing. But it may be during metastasis that the parallels between cancer and wound healing are most pronounced. And more particularly and for the reasons detailed in this paper, any cancer remaining after the removal of a solid tumor, whether found in micrometastatic deposits in the stroma or within the circulation, may be heavily dependent on wound healing pathways for its further survival and proliferation.</p> <p>Discussion</p> <p>If cancer cells can hijack the wound healing process to facilitate their metastatic spread and survival, then the period immediately after surgery may be a particularly vulnerable period of time for the host, as wound healing pathways are activated and amplified after the primary tumor is removed. Given that we often wait 30 days or more after surgical removal of the primary tumor before initiating adjuvant chemotherapy to allow time for the wound to heal, this paper challenges the wisdom of that clinical paradigm, providing a theoretical rationale for administering therapy during the perioperative period.</p> <p>Summary</p> <p>Waiting for wound healing to occur before initiating adjuvant therapies may be seriously compromising their effectiveness, and patients subsequently rendered incurable as a result of this wait. Clinical trials to establish the safety and effectiveness of administering adjuvant therapies perioperatively are needed. These therapies should target not only the residual cancer cells, but also the wound healing pathway utilized by these cells to proliferate and metastasize.</p

Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials

Background Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy. Methods To clarify the relative benefits and risks of dose-intense and standard-schedule chemotherapy in early breast cancer, we did an individual patient-level meta-analysis of trials comparing 2-weekly versus standard 3-weekly schedules, and of trials comparing sequential versus concurrent administration of anthracycline and taxane chemotherapy. The primary outcomes were recurrence and breast cancer mortality. Standard intention-to-treat log-rank analyses, stratified by age, nodal status, and trial, yielded dose-intense versus standard-schedule first-event rate ratios (RRs). Findings Individual patient data were provided for 26 of 33 relevant trials identified, comprising 37 298 (93%) of 40 070 women randomised. Most women were aged younger than 70 years and had node-positive disease. Total cytotoxic drug usage was broadly comparable in the two treatment arms; colony-stimulating factor was generally used in the more dose-intense arm. Combining data from all 26 trials, fewer breast cancer recurrences were seen with dose-intense than with standard-schedule chemotherapy (10-year recurrence risk 28·0% vs 31·4%; RR 0·86, 95% CI 0·82–0·89; p<0·0001). 10-year breast cancer mortality was similarly reduced (18·9% vs 21·3%; RR 0·87, 95% CI 0·83–0·92; p<0·0001), as was all-cause mortality (22·1% vs 24·8%; RR 0·87, 95% CI 0·83–0·91; p<0·0001). Death without recurrence was, if anything, lower with dose-intense than with standard-schedule chemotherapy (10-year risk 4·1% vs 4·6%; RR 0·88, 95% CI 0·78–0·99; p=0·034). Recurrence reductions were similar in the seven trials (n=10 004) that compared 2-weekly chemotherapy with the same chemotherapy given 3-weekly (10-year risk 24·0% vs 28·3%; RR 0·83, 95% CI 0·76–0·91; p<0·0001), in the six trials (n=11 028) of sequential versus concurrent anthracycline plus taxane chemotherapy (28·1% vs 31·3%; RR 0·87, 95% CI 0·80–0·94; p=0·0006), and in the six trials (n=6532) testing both shorter intervals and sequential administration (30·4% vs 35·0%; RR 0·82, 95% CI 0·74–0·90; p<0·0001). The proportional reductions in recurrence with dose-intense chemotherapy were similar and highly significant (p<0·0001) in oestrogen receptor (ER)-positive and ER-negative disease and did not differ significantly by other patient or tumour characteristics. Interpretation Increasing the dose intensity of adjuvant chemotherapy by shortening the interval between treatment cycles, or by giving individual drugs sequentially rather than giving the same drugs concurrently, moderately reduces the 10-year risk of recurrence and death from breast cancer without increasing mortality from other causes. Funding Cancer Research UK, Medical Research Council

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

[Antibiotic preparation in operations on the large intestine. Experimental study].

A controlled study was mounted to assess the possible benefit of a single phlebo administration of 600 mg lincomycin 1 hr prior to colon surgery, in addition to the erythromycin + neomycin combination proposed by Nichols, as a means of constituting a further pharmacological barrier to the spread of anaerobic bacteria. The study currently comprises two groups of 15 patients fully comparable with regard to pathology distribution and randomly assigned to the E.N. and the E.N.L. protocol respectively. Six instances of septic complication have been observed, five in the group prepared with E.N. and 1 prepared with E.N.L. No significance can be attached to the different incidence of complications in the two arms of the study, owing to the small number of cases examined