Complete response

Dynamically, the response of hquid temperature to a step in steam flow is that of a distributed lag, shown in Fig. 8-48. The time required to reach 63 percent complete response, X "t, is essentially the residence time of the fluid in the exchanger, which is its volume divided... 

It should be noticed that the denominators for equations (4.11) and (4.12) are identical. Using the Principle of Superposition, the complete response is given by... 

BCR-ABL tyrosine kinase that is essential for malignant transformation. Cytogenetic responses to IFN-a therapy were seen in 30-40% of the treated patients with complete responses in about 10%. Long term survival can therefore be expected in these patients. In 2000, the BCR-ABL tyrosine kinase inhibitor Imatinib has been introduced for CML therapy and meanwhile has proven more efficient than IFN-a therapy. 

Resubmission = a complete response to an action letter, or submission of an application that has been the subject of a withdrawal or a refusal to file action ... 

An action letter must be issued within 180 days of the start of the review, unless an extension has been agreed with the applicant. If the submission is fully acceptable an Approval Letter is issued. However, if there are problems remaining, the applicant vdll receive a Not Approvable Letter (major problems), or an Approvable Letter (minor problems) in the case of an NDA and a Complete Response Letter in the case of a BLA. These not only summarise the deficiencies that exist but also either outline what steps need to be taken to address the issues or explain why the application carmot be approved. A negative action letter will usually trigger an end-of-review meeting between the FDA and the applicant. This allows the applicant and FDA to discuss and... 

Lok and McMahon 2007), but the ideal outcome is undetectable HBV DNA (< 10-30lU/ml) in highly sensitive real-time PCR-based assays. In HBeAg-positive patients, loss of HBeAg followed by the emergence of anti-HBe antibodies ( e seroconversion) indicates a sustained response to therapy when it persists after treatment cessation. HBs seroconversion (loss of HBsAg and emergence of anti-HBs antibodies) is the most desirable endpoint, as it indicates a complete response with sustained remission from HBV disease. It is rarely achieved with cnrrent therapies. 

MacGowan DJ, Scelsa SN et al (2001) An ALS-like syndrome with new HIV infection and complete response to antiretroviral therapy. Neurology 57(6) 1094-1097 Mahadevan A, Gayathri N et al (2001) Vasculitic neuropathy in HIV infection a clinicopathologi-cal study. Neurol India 49(3) 277-283... 

The response to chemotherapy may be referred to as complete response, partial response, stable disease, or disease progression. 

A cure in oncology implies that the cancer is completely gone, and the patient will have the same life expectancy as a patient without cancer. A complete response (CR) refers to complete disappearance of all cancer for 1 month after treatment. A partial response (PR) is defined as a 50% decrease in tumor diameter along with no new disease for 1 month. The term overall objective response rate refers to the combination of PR and CR. Stable disease refers to tumor that has not grown and has shrunk by less than 25% of the diameter. Disease progression refers to tumor that has spread or the primary tumor has increased in size by 25%. Some cancers, such as leukemia, cannot be measured by size, so biopsy of the bone marrow provides a cellular indication of absence or presence of disease. 

Efficacy Monitor CT scans or other imaging studies, and categorize patient with a complete response (CR), partial response (PR), stable disease (SD), or progressive disease. 

Vinorelbine, a microtubule interactive agent, also has shown impressive response rates in metastatic breast cancer.60 Vinorelbine was approved by the FDA in 1994 for the treatment of non-small cell lung cancer. It is not approved for breast cancer, but response rates to vinorelbine range from 30% to 50%, with an overall 5% complete response rate in phase I and phase II studies in patients with advanced breast cancer. Importantly, paclitaxel, docetaxel, and vinorelbine do not appear to be cross-resistant with anthracyclines, which are arguably considered first-line treatment of metastatic breast cancer. 

Small cell lung cancer typically presents as extensive disease (approximately 60% to 70% of new cases) and progresses very quickly. Small cell carcinomas are very responsive to chemotherapy and radiation. Radiotherapy became the standard in 1969, when a randomized trial showed that it offered the potential for cure, whereas surgery did not.20 For the vast majority of patients, chemotherapy with or without radiotherapy is the treatment of choice. Even after a complete response to therapy, the cancer usually recurs within 6 to 8 months, and survival time following recurrence is typically short ( 4 months). This yields a typical survival rate of 14 to 20 months for limited disease and 8 to 13 months for extensive disease.33 Table 87-6 illustrates the general treatment path of SCLC. 

Although most patients will achieve a complete response initially, more than 50% of cancers will recur within the first 2 years. 

Health care providers use a multimodality approach including surgery and chemotherapy in the initial treatment of ovarian cancer with a curative intent. Although most patients will achieve a complete response initially, more than 50% of cancers will recur within the first 2 years,2,35 Complete response to treatment is defined as no evidence of disease can be detected by physical examination or diagnostic tests, and patient has a normalized CA-125 value. 

FIGURE 91-3. Summary of chemotherapy treatment algorithm for epithelial ovarian cancer. CR, complete response PR, partial response PD, progressive disease. 

In patients who experienced a complete response to first-line chemotherapy and have had greater than a 6-month platinum-free interval, retreatment with a platinum-containing regimen is appropriate. Current National Comprehensive Cancer Network (NCCN) guidelines recommend the combination of carboplatin... 

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. 

Gadducci A, Cosio S, Conte PF, Genazzani AR. Consolidation and maintenance treatments for patients with advanced epithelial ovarian cancer in complete response after first-line chemotherapy a review of the literature. Crit Rev Oncol Hematol 2005 55 153-166. 

Imatinib is a tyrosine kinase inhibitor that produces high complete response rates and is first-line treatment for chronic myelogenous leukemia (CML). 

LL, a 47-year-old man, was diagnosed with high-risk diffuse large cell B-cell non-Hodgkin s lymphoma (NHL) 12 months ago. LL had a complete response to his initial treatment of six cycles of RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). LL is participating in a clinical trial and is randomized to receive a myeloablative autologous HCT TBI days 8 to 5, etoposide day 4, rest day 3, cyclophosphamide day 2, rest day 1, with infusion of autologous PBPC on day 0. 

The FDA Accepts the Complete Response for Clinical Hold of FG-2216/FG-4592 for the Treatment of Anemia, April 2, 2008, http //www.astellas.com/en/corporate/news/ pdf/080402 eg.pdf (accessed July 6, 2010). 

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