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First-line chemotherapy regimens for advanced or metastatic TCC consists of gemcitabine and cisplatin) (GC) or a combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC).
Taxanes or vinflunine have been used as second-line therapy (after progression on a platinum containing chemotherapy).
Immunotherapy such as pembrolizumab is often used as second-line therapy for metastatic urothelial carcinoma that has progressed despite treatment with GC or MVAC.
In May 2016 FDA granted accelerated approval to atezolizumab for locally advanced or metastatic urothelial carcinoma treatment after failure of cisplatin-based chemotherapy. The confirmatory trial (to convert the accelerated approval into a full approval) failed to achieve its primary endpoint of overall survival.
Radiotherapy is commonly used to treat Merkel-cell cancers. The radiotherapy fields used are usually very large so as to cover sufficient areas of skin. This is necessary because of MCC's aggressive local and regional metastatic behavior.
Adjuvant radiotherapy has been shown to be effective in reducing the rates of recurrence and in increasing the survival of patients with MCC. Patients who present with no distant metastases and a negative sentinel lymph node biopsy have a very good prognosis when treated with both surgery and radiotherapy (approximately 90% survival rate at five years).
Metastatic MCC may respond to treatment with chemotherapy and/or radiation, but current multimodal therapies are usually not curative. Intensive treatment can be effective in shrinking the tumor and improving operability when tumors are too large to be removed or located in a place where removal would be difficult or dangerous, or in palliation of signs and symptoms caused by metastatic tumors.
In ES-SCLC, combination chemotherapy is the standard of care, with radiotherapy added only to palliate symptoms such as dyspnea, pain from liver or bone metastases, or for treatment of brain metastases, which, in small-cell lung carcinoma, typically have a rapid, if temporary, response to whole brain radiotherapy.
Combination chemotherapy consists of a wide variety of agents, including cisplatin, cyclophosphamide, vincristine and carboplatin. Response rates are high even in extensive disease, with between 15% and 30% of subjects having a complete response to combination chemotherapy, and the vast majority having at least some objective response. Responses in ES-SCLC are often of short duration, however.
If complete response to chemotherapy occurs in a subject with SCLC, then prophylactic cranial irradiation (PCI) is often used in an attempt to prevent the emergence of brain metastases. Although this treatment is often effective, it can cause hair loss and fatigue. Prospective randomized trials with almost two years follow-up have not shown neurocognitive ill-effects. Meta-analyses of randomized trials confirm that PCI provides significant survival benefits.
Cancers often grow in an unbridled fashion because they are able to evade the immune system. Immunotherapy is a method that activates the person's immune system and uses it to their own advantage. It was developed after observing that in some cases there was spontaneous regression. Immunotherapy capitalises on this phenomenon and aims to build up a person's immune response to cancer cells.
Other targeted therapy medications inhibit growth factors that have been shown to promote the growth and spread of tumours. Most of these medications were approved within the past 10 years. These treatments are:
- Nivolumab
- Axitinib
- Sunitinib
- Cabozantinib
- Everolimus
- Lenvatinib
- Pazopanib
- Bevacizumab
- Sorafenib
- Temsirolimus
- Interleukin-2 (IL-2) has produced "durable remissions" in a small number of patients, but with substantial toxicity.
- Interferon-α
Activity has also been reported for ipilimumab but it is not an approved medication for renal cancer.
More medications are expected to become available in the near future as several clinical trials are currently being conducted for new targeted treatments, including: atezolizumab, varlilumab, durvalumab, avelumab, LAG525, MBG453, TRC105, and savolitinib.
Chemotherapy and radiotherapy are not as successful in the case of RCC. RCC is resistant in most cases but there is about a 4–5% success rate, but this is often short lived with more tumours and growths developing later.
Transitional cell carcinoma (TCC) can be very difficult to treat. Treatment for localized stage TCC is surgical resection of the tumor, but recurrence is common. Some patients are given mitomycin into the bladder either as a one-off dose in the immediate post-operative period (within 24 hrs) or a few weeks after the surgery as a six dose regimen.
Localized/early TCC can also be treated with infusions of BCG into the bladder. These are given weekly for either 6 weeks (induction course) or 3 weeks (maintenance/booster dose). Side effects include a small chance of developing systemic tuberculosis or the patient becoming sensitized to the BCG causing severe intolerance and a possible reduction in bladder volume due to scarring.
In patients with evidence of early muscular invasion, radical curative surgery in the form of a cysto-prostatectomy usually with lymph node sampling can also be performed. In such patients, a bowel loop is often used to create either a "neo-bladder" or an "ileal conduit" which act as a place for the storage of urine before it is evacuated from the body either via the urethra or a urostomy respectively.
A wide variety of chemotherapies options exist for used in advanced (metastatic) NSCLC. These agents include both traditional chemotherapies like cisplatin which indiscriminately target all rapidly dividing cells as well as newer targeted agents which are more tailored to specific genetic aberrations found within a patient's tumor. At present there are two genetic markers which are routinely profiled in NSCLC tumors to guide further treatment decision making: mutations within EGFR and Anaplastic Lymphoma Kinase. There are also a number of additional genetic markers which are known to be mutated within NSCLC and may impact treatment in the future, including BRAF (gene), HER2/neu and KRAS.
Thermal ablations i.e. radiofrequency ablation, cryoablation, microwave ablation are appropriate for palliative treatment of tumor-related symptoms or recurrences within treatment fields. Patients with severe pulmonary fibrosis and severe emphysema with a life expectancy <1 year should be considered poor candidates for this treatment.
Surgery is usually the first treatment that a patient undergoes for Merkel-cell cancer. Lesions usually appear purple-red in color, and there is little else to distinguish this variant of skin cancer from other types. Its identity usually comes as a surprise after surgery and pathologic examination.
As with surgery for most other forms of cancer, it is normal for the surgeon to remove a border of healthy tissue surrounding the tumor. While it has been thought that leaving this margin may not be as critical as it is in the surgical resection of melanoma, studies also reveal that local recurrences are fairly common in MCC near the site of the surgery.
Local or regional lymph nodes are usually removed if the lesion is more than 1 cm in diameter, due to a high risk that they will contain cancer cells (micrometastasis) that could develop into a new tumor or spread further. Sometimes, however, the doctor will first perform a sentinel lymph node biopsy. In this procedure, the doctor injects a dye or radioactive substance near the tumor. This material flows into adjacent lymph nodes, which are identified, removed, and checked for cancer cells, indicating the sites where cancer is most likely to spread (the "sentinel" nodes). This procedure has been demonstrated to be an important prognostic indicator. Results help dictate the use of appropriate adjuvant therapies. Usually, however, surgery alone is insufficient to control Merkel-cell carcinoma.
NSCLCs are usually "not" very sensitive to chemotherapy and/or radiation, so surgery remains the treatment of choice if patients are diagnosed at an early stage. If patients have small, but inoperable tumors, they may undergo highly targeted, high intensity radiation therapy. New methods of giving radiation treatment allow doctors to be more accurate in treating lung cancers. This means less radiation affects nearby healthy tissues. New methods include Cyberknife and stereotactic body radiation therapy(SBRT). Certain patients deemed to be higher risk may also receive adjuvant (ancillary) chemotherapy after initial surgery or radiation therapy. There are a number of possible chemotherapy agents which can be selected however most will involve the platinum-based chemotherapy drug called cisplatin.
Other treatments include percutaneous ablation and chemoembolization. The most widely used ablation techniques for lung cancer are radiofrequency ablation, cryoablation, and microwave ablation. Ablation may be an option for patients whose tumors are near the outer edge of the lungs. Nodules less than 1 cm from the trachea, main bronchi, oesophagus and central vessels should be excluded from RFA given high risk of complications and frequent incomplete ablation. Additionally, lesions greater than 5 cm should be excluded and lesions 3 to 5 cm should be considered with caution given high risk of recurrence. As a minimally invasive procedure, it can be a safer alternative for patients who are poor candidates for surgery due to co-morbidities or limited lung function. A study comparing thermal ablation to sublobar resection as treatment for early stage NSCLC in older patients found no difference in overall survival of the patients. It is possible that RFA followed by radiation therapy has a survival benefit due to synergysm of the two mechanisms of cell destruction.
In cases of LS-SCLC, combination chemotherapy (often including cyclophosphamide, cisplatinum, doxorubicin, etoposide, vincristine and/or paclitaxel) is administered together with concurrent chest radiotherapy (RT).
Chest RT has been shown to improve survival in LS-SCLC.
Exceptionally high objective initial response rates (RR) of between 60% and 90% are seen in LS-SCLC using chemotherapy alone, with between 45% and 75% of individuals showing a "complete response" (CR), which is defined as the disappearance of all radiological and clinical signs of tumor. However, relapse rate remains high, and median survival is only 18 to 24 months.
Because SCLC usually metastasizes widely very early on in the natural history of the tumor, and because nearly all cases respond dramatically to chemotherapy and/or radiotherapy, there has been little role for surgery in this disease since the 1970s. However, recent work suggests that in cases of small, asymptomatic, node-negative SCLC's ("very limited stage"), surgical excision may improve survival when used prior to chemotherapy ("adjuvant chemotherapy").
Photodynamic therapy (PDT) is a new modality for treatment of basal-cell carcinoma, which is administrated by application of photosensitizers to the target area. When these molecules are activated by light, they become toxic, therefore destroy the target cells. Methyl aminolevulinate is approved by EU as a photosensitizer since 2001. This therapy is also used in other skin cancer types. The 2008 study reported that PDT was a good treatment option for primary superficial BCCs, reasonable for primary low-risk nodular BCCs, but a 'relatively poor' option for high-risk lesions.
Radiation therapy can be delivered either as external beam radiotherapy or as brachytherapy (internal radiotherapy). Although radiotherapy is generally used in older patients who are not candidates for surgery, it is also used in cases where surgical excision will be disfiguring or difficult to reconstruct (especially on the tip of the nose, and the nostril rims). Radiation treatment often takes as few as 5 visits to as many as 25 visits. Usually, the more visits scheduled for therapy, the less complication or damage is done to the normal tissue supporting the tumor. Radiotherapy can also be useful if surgical excision has been done incompletely or if the pathology report following surgery suggests a high risk of recurrence, for example if nerve involvement has been demonstrated. Cure rate can be as high as 95% for small tumor, or as low as 80% for large tumors. Usually, recurrent tumors after radiation are treated with surgery, and not with radiation. Further radiation treatment will further damage normal tissue, and the tumor might be resistant to further radiation. Radiation therapy may be contraindicated for treatment of nevoid basal-cell carcinoma syndrome. The 2008 study reported that radiation therapy is a good treatment for primary BCCs and recurrent BCCs, but not for BCCs that have recurred following previous radiation treatment.
Surgery is the mainstay of treatment for clinically localized disease. In feasible cases, a partial cystectomy with "en-bloc" resection of the median umbilical ligament and umbilicus can achieve good results. In progressed stages, radiotherapy seems not to lead to sufficient response rates. However, chemotherapy regimes containing 5-FU (and Cisplatin) have been described to be useful in these cases. In recent years, targeted therapies have been demonstrated to be useful in reports of single cases. These agents included Sunitinib, Gefitinib, Bevacizumab and Cetuximab.
Because LCLC-RP is so rare, no clinical trials have ever been conducted that specifically address treatment of this lung cancer variant. Because LCLC-RP is considered a form of non-small cell lung carcinoma (NSCLC), most physicians adhere to published NSCLC treatment guidelines in rhabdoid carcinoma cases. When possible, radical surgical resection with curative intent is the primary treatment of choice in early stage NSCLC's, and can be administered with or without adjuvant, neoadjuvant, or palliative chemotherapy and/or radiotherapy, depending on the disease stage and performance status of the individual patient.
In numerous clinical trials conducted in NSCLC, several different platinum-based chemotherapy regimens have been shown to be more-or-less equally effective. LCLC's, as a subtype of NSCLC, have traditionally been included in many of these clinical trials, and have been treated like other NSCLC's. More recent trials, however, have shown that some newer agents may have particular effectiveness in prolonging survival of LCLC patients. Pemetrexed, in particular, has shown significant reduction in the hazard ratio for death when used in patients with LCLC. Taxane-based (paclitaxel, docetaxel) chemotherapy was shown to induce a complete and sustained response in a liver metastasis in a case of LCC-RP. A later-appearing metastasis within mediastinal lymph nodes in the same case also showed a durable response to a taxane alone.
There have also been reports of rhabdoid carcinomas expressing vascular endothelial growth factor (VEGF), suggesting that targeted molecular therapy with VEGF blocking monoclonal antibodies such as bevacizumab may be active in these variants. However, evidence suggests that caution must be used when treating a cavitated rhabdoid tumor, one that contains significant components of squamous cell differentiation, or large tumors with containing major blood vessels, due to the potential high risk of life-threatening pulmonary hemorrhage.
A recent study reported a case wherein 2 courses of adjuvant therapy with cisplatin and paclitaxel, followed by oral gefitinib, were used after complete resection. The patient had had no recurrence 34 months later.
As large-volume LCLC-RP may show significant central necrosis and cavitation, prudence dictates that oncologists use extreme caution if contemplating the therapeutic use of bevacizumab, other anti-VEGF compounds, or anti-angiogenesis agents in general, which have been associated with a greatly increased risk of severe hemorrhage and hemoptysis that may be quickly fatal in cavatated pulmonary squamous cell carcinomas. Similar elevated risks have also been noted in tumors located near, or containing, large blood vessels.,
This cancer is typically aggressive, presents at an advanced stage when the cancer has already metastasized, and is resistant to chemotherapy. It therefore poses a significant management challenge. Current treatment options include surgical resection and chemotherapy with a variety of agents, including (but not limited to) ifosfamide, etoposide, carboplatin, and topotecan. A recent study looked at the use of methotrexate, vinblastine, doxorubicin, and cisplatin in 3 patients and saw a partial response and longer survival than historical reports. Carboplatin, gemcitibine, and paclitaxel provided a complete response in a patient with advanced disease. The role of radiation is unclear; some tumors have shown a response to radiation. Due to the apparent propensity for the tumor to spread to the central nervous system, it has been suggested that prophylactic craniospinal irradiation should be considered.
Treatment of invasive carcinoma of no special type (NST) depends on the size of the mass (size of the tumor measured in its longest direction):
- <4 cm mass: surgery to remove the main tumor mass and to sample the lymph nodes in the axilla. The stage of the tumor is ascertained after this first surgery. Adjuvant therapy (i.e., treatment after surgery) may include a combination of chemotherapy, radiotherapy, hormonal therapy (e.g., tamoxifen) and/or targeted therapy (e.g., trastuzumab). More surgery is occasionally needed to complete the removal of the initial tumor or to remove recurrences.
- 4 cm or larger mass: modified (a less aggressive form of radical mastectomy) radical mastectomy (because any malignant mass in excess of 4 cm in size exceeds the criteria for a lumpectomy) along with sampling of the lymph nodes in the axilla.
The treatment options offered to an individual patient are determined by the form, stage and location of the cancer, and also by the age, history of prior disease and general health of the patient. Not all patients are treated the same way.
For treatment purposes, MCACL has been traditionally considered a non-small cell lung carcinoma (NSCLC). Complete radical surgical resection is the treatment of choice.
There is virtually no data regarding new molecular targets or targeted therapy in the literature to date. Iwasaki and co-workers failed to find mutations of the epidermal growth factor receptor (EGFR) or the cellular Kirsten rat sarcoma virus oncogene "K-ras" in one reported case.
Primary treatment for this cancer, regardless of body site, is surgical removal with clean margins. This surgery can prove challenging in the head and neck region due to this tumour's tendency to spread along nerve tracts. Adjuvant or palliative radiotherapy is commonly given following surgery. For advanced major and minor salivary gland tumors that are inoperable, recurrent, or exhibit gross residual disease after surgery, fast neutron therapy is widely regarded as the most effective form of treatment.
Chemotherapy is used for metastatic disease. Chemotherapy is considered on a case by case basis, as there is limited trial data on the positive effects of chemotherapy. Clinical studies are ongoing, however.
Treatment of metastatic breast cancer is currently an active area of research. Several medications are in development or in phase I/II trials. Typically new medications and treatments are first tested in metastatic cancer before trials in primary cancer are attempted.
Another area of research is finding combination treatments which provide higher efficacy with reduced toxicity and side effects.
Experimental medications:
- sorafenib a combined Tyrosine protein kinases inhibitor.
Some patients with metastatic breast cancer opt to try alternative therapies such as vitamin therapy, homeopathic treatments, a macrobiotic diet, chiropractic or acupuncture. There is no evidence that any of these therapies are effective; they may be harmful, either because patients pass up effective conventional therapies such as chemotherapy or anti-estrogen therapy in favor of alternative treatments, or because the treatments themselves are harmful (as in the case of apricot-pit therapy—which exposes the patient to cyanide—or in chiropractic, which can be dangerous to patients with cancer metastatic to the spinal bones or spinal cord. A macrobiotic diet is neither effective nor safe as it could hypothetically induce weight loss due to severe dietary restriction. There is limited evidence that acupuncture might relive pain in cancer patients, but data so far is insufficient to recommend its use outside of clinical trials.
There is free peer support and an online platform to interact with others going through various therapies, including Abraxane.
Treatment and survival is determined, to a great extent, by whether or not a cancer remains localized or spreads to other locations in the body. If the cancer metastasizes to other tissues or organs it usually dramatically increases a patient's likelihood of death. Some cancers—such as some forms of leukemia, a cancer of the blood, or malignancies in the brain—can kill without spreading at all.
Once a cancer has metastasized it may still be treated with radiosurgery, chemotherapy, radiation therapy, biological therapy, hormone therapy, surgery, or a combination of these interventions ("multimodal therapy"). The choice of treatment depends on a large number of factors, including the type of primary cancer, the size and location of the metastases, the patient's age and general health, and the types of treatments used previously. In patients diagnosed with CUP it is often still possible to treat the disease even when the primary tumor cannot be located.
Current treatments are rarely able to cure metastatic cancer though some tumors, such as testicular cancer and thyroid cancer, are usually curable.
Palliative care, care aimed at improving the quality of life of people with major illness, has been recommended as part of management programs for metastasis.
Nasopharyngeal carcinoma can be treated by surgery, by chemotherapy, or by radiotherapy. The expression of EBV latent proteins within undifferentiated nasopharyngeal carcinoma can be potentially exploited for immune-based therapies.
Since Krukenberg tumors are secondary (metastatic), management might logically be driven by identifying and treating the primary cancer. The optimal treatment of Krukenberg tumors is unclear. The role of surgical resection has not been adequately addressed but if metastasis is limited to the ovaries, surgery may improve survival. The role of chemotherapy and/or radiotherapy is uncertain but may sometimes be beneficial.
CUP is a term that refers to many different cancers. For that reason, treatment depends on where the cancer is found, the microscopic appearance of the cancer cells, the biochemical characterization of the cells, and the patient’s age and overall physical condition. In women, who present with axillary lymph node involvement, treatment is offered along the lines of breast cancer. In patients, who have neck lymph node involvement, then treatment is offered along the lines of head and neck cancer. If inguinal lymph nodes are involved, then treatment may be offered along the lines of genitourinary cancer.
If the site of origin is unknown or undiscovered, then the histology of the tumor (e.g., adenocarcinoma, squamous cell or mesenchymal) can usually be identified, and a probable origin may be assumed. When this is possible, then treatment is based on the type of cell and probable origin. Based on histological subtype, combination chemotherapy may be selected. A combination of carboplatin and paclitaxel is often used. Advances techniques such as FISH and tissue of origin testing may also be employed. Germ cell tumors often carry abnormality of chromosome 12, which if identified, directs treatment for metastatic germ cell tumors.
No method is standard for all forms of CUP, but chemotherapy, radiation therapy, hormone therapy, and surgery may be used alone or in combination to treat patients who have CUP. Even when the cancer is unlikely to be cured, treatment may help the patient live longer or improve the patient’s quality of life. Radiation may be used to shrink a variety of local tumors. However, the potential side effects of the treatment must be considered along with the potential benefits.
In CUP to secondary neck nodes, surgery followed by external beam radiotherapy is sufficient.
For CUP with an unfavorable prognosis, treatment with taxanes may provide a slight survival benefit. The uncertainties and ambiguity inherent in a CUP diagnosis may cause additional stress for the patient.
Renal medullary carcinoma is extremely rare and it is not currently possible to predict those individuals with sickle cell trait who will eventually develop this cancer. It is hoped that early detection could result in better outcomes but screening is not feasible.