Overall survival

The therapeutic success is measured by its effect on tumor size and can be described as tumor remission (complete or partial), stable disease, or progression of the tumor. Also, the impact of a therapy is related to time and can be measured as disease free interval, time to progress, or overall survival time. 

The response to erythropoietin products must be monitored closely to prevent adverse effects associated with these agents. The common adverse effects experienced include hypertension and thrombosis. Concomitant drugs with the same adverse-effect profile may increase a patient s risk for these complications. Also, the patient s overall survival may be decreased if the hemoglobin level is titrated to above the recommended 11 to 12 g/dL (110-120 g/L or 6.82-7.44 mmol/L) value. Therefore, it is important to follow the dosing and titration scheme recommended by the NCCN and summarized in... 

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. 

For early-stage diffuse, aggressive NHL, combined-modality therapy was tested versus a longer course of chemotherapy.22 Overall survival favored the CHOP/radiation arm for 5 years (82% versus 72%). There was a trend toward increased toxicity, particularly hematologic and cardiac toxicity, in the CHOP alone arm. The results of this trial have established combined-modality therapy as first-line treatment for early-stage NHL. Unique presentations of NHL, such as CNS primary disease, may incorporate radiation into treatment algorithms.23... 

The histology of the disease is a prognostic factor. For instance, clear-cell and undifferentiated tumors do not respond as well to chemotherapy.2 The extent of residual disease and tumor grade are also predictive of response to chemotherapy and overall survival.2 There are other prognostic factors that may predict how well a patient will respond to adjuvant chemotherapy. 

Overall survival is affected by the success of the initial surgery to debulk the tumor to less than 1 cm of disease and response to first-line chemotherapy. The CA-125 level should be monitored with each cycle, and at least a 50% reduction in CA-125 after four cycles of taxane/platinum chemotherapy is related to an improved prognosis. Patients who achieve a complete response should have follow-up examinations every 3 months, including CA-125 determination, physical examination, pelvic examination, and appropriate diagnostic scans (e.g., CT scan, MRI, or PET scan) and should be evaluated for the detection of disease. Evaluate patients for resolution of any residual chemotherapy-related side effects, including neuropathies, nephrotoxicity, ototoxicity, myelosuppression, and nausea/vomiting. 

The major prognostic factors in newly diagnosed AML are age, sub-type (FAB M2), and chromosome status. Older adults with AML (greater than 60 years), in comparison with younger patients with the same disease, have a dismal prognosis and represent a distinct population in terms of disease biology, treatment-related complications, and overall survival. These older patients have a higher incidence of unfavorable chromosomal abnormalities, such as aberrations of chromosomes 5,7, or 8, and fewer abnormalities that are associated with a more favorable outcome, such as t(8 21) or inv(16) (see Table 92—6).9... 

The treatment of CNS leukemia has had a remarkable impact on the overall survival for childhood ALL. While also effective at reducing the incidence of CNS relapse in adults, CNS prophylaxis has not shown measurable effects on overall survival.10... 

With increased success in pediatric clinical trials, the overall survival rate for pediatric cancers has increased significantly over the last 35 years. For certain disease states, the overall survival rate for specific pediatric malignancies is now up to 80%. Unfortunately, the consequences of success are that approximately two-thirds of childhood cancer survivors have at least one chronic or late-occurring complication of treatment. Long-term follow-up of survivors treated decades ago also has revealed very late sequelae.24... 

Chemotherapy does not improve overall survival in early-stage chronic lymphocytic leukemia (CLL). 

The primary goals in the treatment of CLL are to provide palliation of symptoms and to improve overall survival. Since the current treatments for CLL are not curative, reduction in tumor burden and improvement in disease symptoms are reasonable end points, particularly in older patients. A response to therapy can be evaluated by a resolution of lymphadenopathy... 

Chemotherapy does not improve overall survival in early-stage CLL In addition, deferring therapy until a patient becomes symptomatic does not alter overall survival.19,20 For this reason, the notion of watch and wait is considered reasonable for older patients with indolent disease. 

Combination therapy may provide improvement in longterm disease-free survival. The combination of fludarabine, cyclophosphamide, and rituximab improves CR rates compared with fludarabine alone (70% versus 20%) but at the expense of increased infections.28,29 Combinations of fludarabine and alemtuzumab are also being investigated, with the hope of improving overall survival.21... 

The primary goal in the treatment of multiple myeloma is to decrease tumor burden and minimize complications associated with the disease. A watch and wait approach is an option for asymptomatic patients who have no lytic lesions in the bone. Once symptoms occur, treatment is required. Chemotherapy can be used to reduce tumor burden in patients with symptomatic disease, but increasingly, immunomodula-tors such as thalidomide and dexamethasone are initial therapy. Almost all patients will become refractory to initial treatment and will require the use of salvage therapies such as bortezomib. Autologous stem cell transplantation prolongs overall survival in patients who can tolerate high-dose chemotherapy and may be the treatment of choice for many patients. 

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 evaluation of HDI for high-risk MM, data from a pooled analysis of four major clinical trials that randomized patients to either HDI or observation recently became available. The results showed improved relapse-free survival, with an approximate 10% reduction in the risk of recurrence, but no effect on overall survival in patients receiving HDI.48 A pooled analysis of several high-dose IFN trials and a trial comparing HDI with vaccine (E1694) also confirmed a reduction in the risk of recurrence with HDI without significant improvement in overall survival.49,50... 

CMF regimen is a combination of cyclophosphamide, MTX, and 5-FU, and represents one of the treatments of choice for women with non-metastatic breast cancer, significantly increasing disease-free and overall survival. A recent report in a... 

Lenz H-J, Leichman CG, Danenberg KD, Danenberg PV, Grashen S, Cohen H et al. Thymidylate synthase mRNA level in adenocarcinoma of the stomach a predictor for primary tumour response and overall survival. J Clin Oncol 1995 14 176-182. 

ATM-deficient cell lines were found to be sensitive to olaparib [53]. In xenograft studies using ATM-deficient Granta-519 cells, olaparib was shown to decrease tumor growth and prolong overall survival by 42%. 

Pharmacokinetic studies in patients yielded an estimated product half-life of approximately 20 days (11-50 days range) and the product clearance was found to be variable according to body weight, gender and tumour burden. Safety and efficacy were established by three randomized, controlled trials. The first study was a randomized double-blind trial involving 813 patients. The primary end-point measured was overall survival, which was extended from a median of 15.6 months to 20.3 months. 

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