Time to progression

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. 

Clinical trials combining chemotherapy and immunotherapy are based on the observations of independent clinical activity of each of these treatment modalities in treating metastatic MM. This combination is known as biochemotherapy. Only one phase III clinical trial showed significant improvement in response rate, time to progression, and median survival favoring the biochemotherapy arm versus the combination-chemotherapy arm.59 Currently, the use of biochemotherapy is not justified outside a clinical trial in patients with stage IV MM.53,58,60... 

Ixabepilone, a microtubule stabilizing agent, is indicated as monotherapy or in combination with capecitabine in MBC patients who have previously received an anthracycline and a taxane. Response rates and time to progression were increased with combination therapy as compared with capecitabine alone. Adverse effects include myelosuppression, peripheral neuropathy, and myalgias/arthralgias. 

Trastuzumab, a monoclonal antibody that binds to HER2, produces response rates of 15% to 20% when used as a single agent and increases response rates, time to progression, and OS when combined with chemotherapy. It has been studied in doublet (taxane-trastuzumab vinorelbine-trastuzumab) and triplet (trastuzumab-taxane-platinum) combinations but the optimum regimen is unknown. 

Lapatinib, a tyrosine kinase inhibitor that targets both HER2 and the epidermal growth factor receptor, improved response rates and time to progression in combination with capecitabine, as compared to capecitabine alone, in patients previously treated with an anthracycline, taxane, and trastuzumab. The most common adverse events were rash and diarrhea. 

Muitipie (two) ways to win — response rate, time to progression... 

Eulvestrant has been evaluated in two randomised phase III trials in postmenopausal women with advanced disease after progression on prior antiestrogen therapy. In both trials, fulvestrant was at least as effective as anas-trozole. In a prospectively designed combined analysis of the results from both trials, median time to progression (TTP) was 5.5 months for fulvestrant versus 4.1 months for anastrozole [172]. Eulvestrant and tamoxifen have been compared as first-line treatments in a trial including post-menopausal women with advanced breast cancer. In this study, the between-treatment difference was non-significant (median TTP 6.8 versus 8.3 months) [173]. 

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... 

Recent review papers have covered in detail the available cUnical results with the mXOR inhibitors [151,156]. Overall, the compounds are well tolerated and may induce prolonged stable disease and increase time to progression in a subset of cancer patients. In particular, promising activity has been reported for CCl-779 in patients with mantle cell non-Hodgkin s lymphoma [151]. 

Patients treated X 2 yr had significantly longer time to progression of disability compared with placebo group... 

F. Role in therapy In untreated HER2-overexpressing metastatic breast cancer, the addition of Herceptin to paclitaxel increases response rates and time to progression it... 

E. Therapeutic response Intravitreal Vitravene therapy is effective in delaying disease progression in AIDS patients with refractory or newly diagnosed CMV retinitis depending on the patient population, the median time to progression has ranged from 2 to 11 weeks. 

In addition, those with the HH genotype showed a longer period of time to progression compared with those with the R allele, (445 days in the HH genotype group vs. 158 days in the HR or RR genotype groups). 

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