The cancer journal
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For most clinical oncologists trained before the 1990s, a 20% or greater response rate is the convention for a drug to be considered active in phase II studies. However, this no longer holds true with several targeted therapies repeatedly achieving the regulatory criteria of progression-free and overall survival benefit with considerably lower objective response rates but a sizeable proportion of patients having stable disease. Considerable skepticism persists as to the value of stable disease as a valid outcome in early clinical trials of new agents. ⋯ Continued uncertainty of the value of stable disease is based on the lack of precision in defining this as a meaningful outcome. With the term stable disease encompassing a broad range from <20% enlargement to <30% reduction using standard response criteria response evaluation criteria in solid tumors, what one refers to as stable disease is open to diverse interpretation. The evidence that stable disease is a valid end point in many recent clinical trials is therefore discussed in this review and along with contemporary methods that bring some accuracy to the interpretation of stable disease within the context of clinical trial results.
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Phase II clinical trials have long been used to screen new cancer therapeutics for antitumor activity ("efficacy") worthy of further evaluation. Traditionally, the primary end point used in these screening trials has been objective response rate (RR), with the desired rate being arbitrarily set by the researchers before initiation of the trial. For cytotoxic agents, especially in common tumor types, response has been a reasonably robust and validated surrogate of benefit. ⋯ Researchers have postulated that these novel agents, as a class, may not induce significant regression of tumors, and that the use of RR as an end point for phase II studies will result in false negative results, and point out that not all available data is used in making the decision. Others have pointed out that even novel agents have proven unsuccessful in pivotal trials if objective responses are not demonstrated in early clinical trials. We review here the historical and current information regarding objective tumor response.
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Significant improvements in the understanding of the biologic behavior of peritoneal surface malignancies in addition to the combination of peritonectomy procedures that allow complete eradication of macroscopic peritoneal disease and hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of surgery, directed at residual microscopic disease, have change the therapeutic strategy from a palliative approach to a curative intent in a selected group of patients with peritoneal carcinomatosis. The rationale for adding HIPEC is supported by the strong pharmacological advantage over systemic therapy. Because of the peritoneal-plasma barrier, intraperitoneal administration of chemotherapy results in intraperitoneal levels that are 20 to 1000 times higher than plasma levels. ⋯ This synergism occurs only at the interface of heat and body tissue at the peritoneal surface. However, despite the wider acceptance to combine extensive cytoreductive surgery with intraoperative intraperitoneal heated chemotherapy, the specifics of the HIPEC administration continue to lack uniformity. The most recent consensus statement issued by the Peritoneal Surface Oncology Group International after the 2006 meeting in Milan concluded that the debate on the best method to deliver HIPEC is still open, and as a group, we declared that there is no sufficient evidence in the literature confirming the superiority of one technique over the other in terms of outcome, morbidity, and safety to the personnel in the operating room.
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Evidence for the efficacy of cytoreductive surgery, combined with hyperthermic intraperitoneal chemotherapy (HIPEC), in the treatment of peritoneal carcinomatosis is accumulating. Many centers around the world now have considerable experience of the complex techniques required to achieve complete cytoreduction with the administration of HIPEC. ⋯ A number of specialized centers have studied the factors that influence perioperative complications and mortality and have demonstrated impressive reductions in morbidity and mortality over time. However, for this treatment to be accepted as standard of care, teams undertaking this treatment strategy must aim to minimize morbidity and mortality by learning from the experience of established centers and using the "global learning curve."
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Chronic pain is a frequent complication of cancer and its treatments and is often underreported, underdiagnosed, and undertreated. Pain in cancer survivors is caused by residual tissue damage from the cancer and/or the cancer therapy. ⋯ Comfort and function are optimized in cancer survivors by a multidisciplinary approach using an individually tailored combination of opioids, coanalgesics, physical therapy, interventional procedures, psychosocial interventions, and complementary and alternative modalities. Management of chronic pain must be integrated into comprehensive cancer care so that cancer patients can fully enjoy their survival.