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Cancer #4 As treatment for
Hormonal therapy has also played an important role in the treatment of breast and prostate cancer. In the metastatic setting, use of hormonal therapy when appropriate and often combined with chemotherapy has likely improved median overall survival to approximately 2 years with reports of long-term survivors of 8 years and longer Gennari et al.
Adjuvant hormonal therapy, depending on whether tamoxifen or an aromatase inhibitor AIs is used tends to be associated with musculoskeletal discomfort, early osteoporosis and increased cardiac events for AIs versus increased venous thromboembolic events and uterine hyperplasia rarely malignancy with tamoxifen Mincey et al. With regards to prostate cancer, in both the adjuvant setting for locally advanced disease and in overt metastatic disease, androgen deprivation therapy is associated with an improvement in overall survival Nguyen et al.
Side-effects from androgen deprivation therapy include sexual dysfunction, hot flashes, early osteoporosis complicated by bone fractures and loss of lean body mass Shahinian et al.
The examples described above demonstrate that conventional cytotoxic chemotherapy has an important role in the management of patients diagnosed with cancer, but the use of these agents is clearly associated with long-term toxicities in long-term survivors. Moreover we can anticipate that further improvements in cancer survival related to the increasing use of cytotoxic chemotherapies in more potent and effective regimens, will also lead to increasing numbers of patients being affected by the cancer treatment-related long-term toxicities.
Present and future challenges include identifying the appropriate dosing of cytotoxic agents and other components of multimodal anti-cancer treatment regimens to maximize therapeutic efficacy while limiting both acute and long-term side-effects.
Indeed a number of trials are ongoing to answer these questions but these are statistically complex trials that require a large number of subjects as well as extended follow up several years to accurately capture long-term toxicities. An important group of patients which require special consideration is the rapidly expanding population with metastatic incurable disease, where chemotherapy treatment is frequently used to control cancer indefinitely.
The sequential use of several different chemotherapy agents is becoming increasingly common to overcome tumor resistance as it emerges e. Nevertheless these patients often accumulate considerable exposure to multiple chemotherapeutic agents, and are thus at high risk of cumulative treatment-related side-effects.
Paradoxically patient ability or willingness to tolerate such side-effects, rather than uncontrolled disease, or absence of potential active anti-cancer treatments, may rapidly become the limiting factor for treatment success in this population.
Although the use of cytotoxic chemotherapy has had some notable success as described above, a significant proportion of patients suffering from cancer either do not respond to conventional chemotherapy or relapse after treatment. In addition, several cancer types, such as melanoma, renal cell carcinoma, hepatocellular carcinoma, and gastrointestinal stromal tumors GIST have very limited response to conventional cytotoxic chemotherapy.
For these cancers, patients have frequently received treatments with minimal benefit but significant toxicity, in the hope that this would slow disease progression in some cases. More recently the ability to characterize specific gene mutations in different cancers, and a greater biological understanding of the cellular events and pathways driving carcinogenesis, has led to the development of targeted agents and immunotherapeutics.
These new therapies appear to offer considerable advantages in delivering growth inhibitory or cytotoxic effects in a much more cell-specific manner. Furthermore these drugs do not induce the same profile of acute toxicities such as myelosuppression and nausea and vomiting which accompany many of the conventional non-targeted cytotoxic drugs. As described below some of the newer targeted agents have proven highly effective anti-cancer treatments, and have already delivered startling improvements in survival for certain cancers.
However, many of the cellular pathways which are disrupted in cancer cells and targeted by these newer treatments, are also of fundamental importance to normal growth or homeostasis in all cells. Furthermore typical treatments are prolonged, extending over many months or years.
Both these factors suggest there is a reasonable chance that the targeted agents still carry a risk of effects in other non-cancer cells. In many cases there is still not enough clinical experience with these drugs to establish precise or robust long-term toxicity profiles, but as detailed below, many of these agents do have unforeseen shorter term side-effects and induce variable degrees of morbidity as a result.
The impact of Imatinib on outcomes in chronic myelogenous leukemia CML is perhaps the best example of the marked improvements that targeted treatments have made in cancer treatment. Imatinib, one of a family of tyrosine kinase inhibitor TKI molecules has proven highly effective in the treatment of CML and has had a dramatic impact on the course of this disease.
Prior to imatinib, the majority of patients diagnosed with CML in the chronic phase would generally progress to a blastic phase within 5 years of diagnosis and most would die.
It is now estimated that the majority of patients with CML have a normal life expectancy Gambacorti-Passerini et al. For the most part, however, these patients are not considered cured, rather imatinib maintains a very low level of CML cells and lifelong therapy may be required. Many consider imatinib to be the most successful of all the targeted therapies discovered to date against cancer.
This success largely relates to the relatively simple molecular biology of CML, which unlike most other cancers, is associated with one dominant single gene rearrangement resulting in its neoplastic potential. Imatinib has also been found to be quite active in treating GIST both in the adjuvant and locally advanced as well as metastatic setting Blanke et al.
GIST frequently overexpresses c-kit and imatinib cross-reacts and significantly inhibits this tyrosine kinase receptor, and as a result relapse-free survival and progression-free survival have significantly improved in this previously chemotherapy-refractory disease. In advanced disease or metastatic disease, complete responses are rare but long-term stable disease on imatinib, can be maintained for 2—3 years.
In the adjuvant setting, it is presently not clear how long patients should remain on imatinib post-resection and some data suggests the longer the better Joensuu et al. Interestingly, even with the relative selectivity of imatinib, patients still suffer from a number of side-effects that are likely from cross-reactivity of the agent with other tyrosine kinases on healthy tissues.
The side-effects of imatinib are generally considered mild but may persist for as long as the patient remains on therapy and have been associated with a diminished quality of life Efficace et al.
Side-effects include but are not limited to fatigue, diarrhea, nausea and vomiting along with muscle cramps, musculoskeletal pains, rash and edema. Other toxicities include cytopenias, hepatotoxicity, and cardiac toxicity. Long-term toxicities of imatinib and the long-term consequences of the chronic side-effects described above are not yet known but it should be noted that after 8 years of follow-up in patients being treated for CML, no increased risk of secondary cancers has been described Verma et al.
In the last decade, a number of other TKIs have been developed and have shown some success in treating lung cancers. Erlotinib and gefitinib are TKIs that target a mutated active epidermal growth factor receptor that is implicated in approximately. First-line treatment with either gefitinib or erlotinib, in patients harboring an EGFR mutation with stage IV disease is associated with an approximately 5—6 month improvement in progression-free survival when compared to conventional chemotherapy Mok et al.
Benefit in overall survival has been difficult to demonstrate given many trials allowed cross-over and the majority of patients went on to get 2nd line therapy. Toxicities reported to date include fatigue, diarrhea, and rash along with hepatic toxicity and rare events of hepatic failure and interstitial pneumonitis. ALK is predominantly present in young non-smoking patients.
Similar to other TKIs, side-effects associated with crizotinib include fatigue, diarrhea, nausea, and vomiting which are rarely severe but there are reports of life-threatening hepatotoxicity and interstitial pneumonitis Ou et al.
As with gefitinib and erlotinib, data regarding crizotinib associated long-term side-effects is very limited given the short period of time they have actually been approved for treatment. With limited efficacy of conventional chemotherapy, targeted therapy has been the predominant focus in renal cell cancers RCCs in particular for clear cell renal cancers. Two classes of agents, TKIs predominantly inhibiting vascular endothelial growth factor tyrosine kinases, vascular endothelial growth factor receptor VEGFR , but most are multi-targeted TKI and mammalian target of rapamycin mTOR inhibitors are the key players.
Most patients with metastatic RCC will be started on one of these classes of agents often resulting in either stability of disease or some degree of partial response. In almost all cases resistance eventually develops, generally within 8 months, and 2nd line therapy with a different agent either in the same class or different class i.
The majority of patients inevitably remain on such therapies lifelong. The VEGFR inhibitors tend to have a number of associated toxicities but to date those reported are mostly for sunitinib and sorafenib simply because the other agents have less available data.
Side-effects include hypertension, an increase in arterial thromboembolic events, thyroid dysfunction, cutaneous toxicity, cardiotoxicity, hepatotoxicity, and skeletal muscle wasting Motzer et al. Although controversial, pre-clinical studies in mice have raised concerns that, sunitinib, a multi-targeted TKI which inhibits VEGF signalling may lead to paradoxical enhancement of tumor metastatic growth in some tumor models Iacovelli et al.
It should be stressed, however, that this potential drawback of sunitinib has not been demonstrated in humans.
Everolimus can result in severe lymphopenia, hyperglycemia, and stomatitis Motzer et al. Interstitial pneumonitis is reported to occur anywhere between 0. For both classes, a description of long-term side-effects is limited by their short duration of time in use.
Targeted therapy agents also include a number of monoclonal antibodies. Examples include trastuzumab, bevacizumab, panitumumab, and cetuximab. It has also been shown to improve overall survival in women suffering from metastatic disease Slamon et al. As mentioned previously, the VEGFR pathway is believed to play an important role in a variety of cancers.
Bevacizumab is a monoclonal antibody against the ligand of VEGFR, and its use has been shown to increase overall survival by approximately 4 months in metastatic colon cancer when used in combination with irinotecan Hurwitz et al. However, a notable increase in grade three and four adverse reactions associated with bevacizumab were also seen which include hypertension, bowel perforation, arterial thromboembolic events, impaired wound healing, and bleeding events Kozloff et al.
Addition of bevacizumab to 5-FU-based chemotherapy in the adjuvant setting has not shown any benefit. Panitumumab and cetuximab are anti-EGFR antibodies that have been shown to increase overall survival in metastatic colon cancer by approximately 5 months in chemotherapy refractory metastatic colon cancer Van Cutsem et al.
Adverse reactions from these antibodies include injection reactions, rash, diarrhea, venous thromboembolic events, and electrolyte abnormalities. Similarly to bevacizumab, addition of either antibody in addition to standard combination chemotherapy has not shown any benefit in the adjuvant setting. For the last 30 years or more attempts to use conventional cytotoxic chemotherapy in the treatment of malignant melanoma resulted in minimal benefit. Two recent major advances in melanoma include the development of a family of TKIs termed Braf inhibitors, and a breakthrough immunotherapeutic agent referred to as ipilimumab.
Both have demonstrated significant benefit in overall survival in patients with metastatic melanoma Hodi et al. Studies in the adjuvant setting, however, are ongoing. Braf inhibitors target mutated Braf tyrosine kinase receptors. Unfortunately, resistance eventually develops in between 6 and 12 months for the majority of patients. Ipilimumab is an anti-CTLA-4 antibody that results in the stimulation of an immune response against melanoma. Side-effects of Braf inhibitors include arthralgia, fatigue, rash and an increase in the number of squamous cell carcinomas and keratoacanthomas.
Side-effects from ipilimumab are predominantly related to an inflammatory type autoimmune response on normal body tissues and include enterocolitis, hepatitis, dermatitis, and endocrinopathies. Targeted therapy is heralded by many as the holy grail of cancer treatment, the best example of which is imatinib in the treatment of CML.
In some instances, however, targeted therapies have fallen short of expectations. Despite showing an improvement in progression free and overall survival, resistance to these agents can develop sometimes within a short time of initiation of therapy. The limited efficacy of these agents in some circumstances likely reflects less on the lack of sophistication of the targeted agents and more on the genetic instability of tumors and the presence of tumor subclones which develop resistance or are inherently resistant to these therapies.
Further genetic characterization of tumors may help to ensure that the right therapy is used in the right patient. Additionally, a number of these targeted therapies have important side-effect profiles, some being associated with pulmonary fibrosis, gastrointestinal toxicity, hepatotoxicity, cardiomyopathy, and other cardiovascular complications.
Whilst these may well be tolerable or acceptable in the short term, where patients are required to remain on such therapies lifelong the impact on function and quality of life may be more difficult to sustain. Despite the many promising and exciting advances in this area of cancer therapeutics there are also many areas of uncertainty including whether the efficacy demonstrated by imatinib in CML can ever be replicated with other agents in other cancer types; and what the long-term health consequences of remaining on these types of therapies will be.
Meanwhile, though optimum treatment regimens and dosing schedules using targeted therapies are still to be established, lifelong treatment for many patients seems to be a likely outcome. Hence the development of new and highly effective targeted anti-cancer therapies, also brings with it new challenges: Addressing these challenges will be vital to the continued success of this collective war on cancer.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. National Center for Biotechnology Information , U. Journal List Front Pharmacol v. Published online May 7. Palumbo , Petr Kavan , Wilson H. Author information Article notes Copyright and License information Disclaimer. Received Jan 14; Accepted Apr This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
This article has been cited by other articles in PMC. Abstract In the last half of the century, advances in the systemic therapy of cancer, including chemotherapy, hormonal therapy, targeted therapy, and immunotherapy have been responsible for improvements in cancer related mortality in developed countries even as the population continues to age.
Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Patients with initially unresectable colorectal liver metastases: Cancer 79 — [ PubMed ] Aleman B. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer.
Chemotherapeutic adjuvant treatment for osteosarcoma: Cancer 47 — [ PubMed ] Bacci G. High grade osteosarcoma of the extremities with lung metastases at presentation: Acute myeloid leukemia after breast cancer: Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT.
Analysis of risk factors for cisplatin-induced ototoxicity in patients with testicular cancer. Late-occurring stroke among long-term survivors of childhood leukemia and brain tumors: Risk of heart failure in breast cancer patients after anthracycline and trastuzumab treatment: Observational study of prevalence of long-term Raynaud-like phenomena and neurological side effects in testicular cancer survivors. Morbidity and mortality in long-term survivors of Hodgkin lymphoma: Cancer 5 65—72 [ PubMed ] Chapman P.
The impact of new chemotherapeutic and hormone agents on survival in a population-based cohort of women with metastatic breast cancer. Cancer — [ PubMed ] Choueiri T. E, Bell- munt J. Risk of arterial thromboembolic events with sunitinib and sorafenib: Decreased adult height in survivors of childhood acute lymphoblastic leukemia: Do adjuvant aromatase inhibitors increase the cardiovascular risk in postmenopausal women with early breast cancer?
Meta-analysis of randomized trials. For this reason, ask your doctor for a referral to a team of doctors with extensive experience in treating bone tumors before your biopsy. If your doctor confirms a diagnosis of bone cancer, he or she tries to determine the extent stage of the cancer because that will guide your treatment options.
Factors to be considered include:. The stages of bone cancer are indicated by Roman numerals, ranging from 0 to IV. The lowest stages indicate that the tumor is smaller and less aggressive.
By stage IV, the cancer has spread to other parts of the body. The treatment options for your bone cancer are based on the type of cancer you have, the stage of the cancer, your overall health and your preferences. Different bone cancers respond to different treatments, and your doctors can help guide you in what is best for your cancer. For example, some bone cancers are treated with just surgery; some with surgery and chemotherapy; and some with surgery, chemotherapy and radiation therapy.
The goal of surgery is to remove the entire cancerous tumor. In most cases, this involves special techniques to remove the tumor in one single piece, along with a small portion of healthy tissue that surrounds it. The surgeon replaces the lost bone with some bone from another area of your body, with material from a bone bank or with a replacement made of metal and hard plastic.
Bone cancers that are very large or located in a complicated point on the bone may require surgery to remove all or part of a limb amputation. As other treatments have been developed, amputation is becoming less common. If amputation is needed, you'll likely be fitted with an artificial limb and go through training to learn to do everyday tasks using your new limb. Chemotherapy uses strong anti-cancer drugs, usually delivered through a vein intravenously , to kill cancer cells.
However, this type of treatment works better for some forms of bone cancer than for others. For example, chemotherapy is generally not very effective for chondrosarcoma, but it's an important part of treatment for osteosarcoma and Ewing sarcoma. Radiation therapy uses high-powered beams of energy, such as X-rays, to kill cancer cells. During radiation therapy, you lie on a table while a special machine moves around you and aims the energy beams at precise points on your body. Radiation therapy is often used before an operation because it can shrink the tumor and make it easier to remove.
This, in turn, can help reduce the likelihood that amputation will be necessary. Radiation therapy may also be used in people with bone cancer that can't be removed with surgery.
After surgery, radiation therapy may be used to kill any cancer cells that may be left behind. For people with advanced bone cancer, radiation therapy may help control signs and symptoms, such as pain. Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this disease. A cancer diagnosis can be overwhelming. With time you'll find ways to cope with the distress and uncertainty of cancer. Until then, you may find it helps to:.
If you have any signs and symptoms that worry you, start by making an appointment with your family doctor. If your doctor suspects you may have bone cancer, you may be referred to a specialist. Bone cancer is often treated by a team of specialists that may include:. Because appointments can be brief, and because there's often a lot of ground to cover, it's a good idea to be well-prepared.
Preparing a list of questions for your doctor can help you make the most of your time together. List your questions from most important to least important in case time runs out. For bone cancer, some basic questions to ask your doctor include:. In addition to the questions that you've prepared to ask your doctor, don't hesitate to ask other questions during your appointment.
Pharmaceutical Treatment of the Cancer Pain Patient
4. Ramp up the cancer patient to do at least minutes of exercise a day, even if it is lifting Understanding the treatment of stage III versus stage IV cancers. New cell-based immunotherapy drugs are changing the way certain cancers are treated at a small number of FDA-approved centers, with the. When staging head and neck cancer, the pathologist determines where Stage II: The head and neck tumor measures cm across, and no cancer cells are.