Survival benefit

It is important to note that the magnitude of survival benefit for chemotherapy appears to be small, with an absolute reduction in mortality of only 5% at 10 years for patients with negative axillary lymph nodes and 10% for patients with positive axillary lymph nodes. In addition, there is currently no means to identify patients who will attain this survival benefit. However,... 

Until recently, there was little evidence that the response or survival benefit from one endocrine therapy was clearly superior to that achieved with other therapies. Given this equality in efficacy, the choice of a particular endocrine therapy was based primarily on toxicity (Table 86-8). Based on these criteria, tamoxifen is the preferred initial agent when metastases are present. An exception to this occurs when the patient is receiving adjuvant tamoxifen at the time or within 1 year of occurrence of metastatic disease. 

The most recent meta-analysis of 27 randomized trials in 8275 patients (4803 treated with flutamide, 1683 treated with nilutamide, and 1784 treated with cyproterone) comparing maximal androgen blockade with conventional medical or surgical castration showed a small survival benefit at 5 years for those treated with flutamide or nilutamide (27.6%) compared with those treated with castration alone (24.7% p = 0.0005).40... 

In an attempt to reduce relapse rate and late toxicity, combined-modality therapy using lower doses of radiation and an abbreviated course of chemotherapy has been evaluated.16 The goal of decreased relapse rate has been achieved, but no overall survival benefit has been documented. A limitation of this approach is exposing patients to the additive toxicities of chemotherapy. Trials that have investigated this approach typically have incorporated between two and four cycles of a standard regimen for HL, such as ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) with involved-field radiation. At present, combined-modality therapy is considered to be a standard of care for stage I/II HL. 

Combination chemotherapy or biochemotherapy increases toxicity significantly without offering overall survival benefit thus they are not standard of care for stage IV melanoma. 

In the case of thrombosis-related SVCS, anticoagulation is controversial because there is a lack of survival benefit. However, thrombolytics (e.g., alteplase) and anti coagulation with heparin and warfarin may be beneficial in patients with thrombosis owing to indwelling catheters if it is used within 7 days of onset of symptoms, although catheter removal maybe required. 

Target doses associated with survival benefits in clinical trials. 

Because of their negative inotropic effects, /J-blockers should be started in very low doses with slow upward dose titration to avoid symptomatic worsening or acute decompensation. Patients should be titrated to target doses when possible to provide maximal survival benefits. However, even lower doses have benefits over placebo, so any dose is likely to provide some benefit. 

Survival benefit for adjuvant chemotherapy in stage I and II breast cancer is modest. The absolute reduction in mortality at 10 years is 5% in nodenegative and 10% in node-positive disease. 

Erlotinib has been approved by the FDA for second- or third-line treatment of NSCLC [45], and in combination with gemcitabine as first-hne therapy for pancreatic cancer [46]. Since the majority of human studies with erlotinib have been in NSCLC, the clinical discussion will focus on this indication. When dosed oraUy once a day at 150mg/day in an uncontrolled phase II study, erlotinib resulted in a 12% objective response rate in second-or third-hne NSCLC patients [47,48]. In first-hne NSCLC, phase III studies of standard-of-care with or without erlotinib failed to show a chnical benefit in objective response rate, time to progression, or survival for the erlotinib-treated group. However, in a large placebo-controlled phase III trial, erlotinib provided a clear survival benefit as single agent in second- or third-hne treatment of NSCLC, which subsequently led to FDA approval [45,49]. In that trial, patients were randomized to receive erlotinib in addition to supportive... 

Postoperative BCNU offers an additional modest survival benefit to radiation therapy only (BTCG 7201 and 7501). 

Cox JD, Azamia N, Byhardt RW, et al. A randomized phase I/II trial of hyperfractionated radiation therapy with total doses of 60.0 Gy to 79.2 Gy Possible survival benefit with greater than or equal to... 

Von Pawel J, Von Roemeling T. Survival benefit from Tirazone (tirapazamine) and cisplatin in advanced non small cell lung cancer (NSCLC) patients Final results from the phase III CATAPULT trial. Proc Am Soc Clin Oncol 1998 17 454a (abstr 1749). 

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