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Oncology > Carcinomas of the Lung and Other Intrathoracic Carcinomas
Extrapulmonary Small Cell Carcinoma
Article Last Updated: Oct 14, 2008
AUTHOR AND EDITOR INFORMATION
Section 1 of 9  
Author: Irfan Maghfoor, MD, Consulting Oncologist, Department of Oncology, King Faisal Specialist Hospital and Research Center, Saudi Arabia
Irfan Maghfoor is a member of the following medical societies: American Society of Hematology
Editors: Robert C Shepard, MD, FACP, Associate Professor of Medicine in Hematology and Oncology at University of North Carolina at Chapel Hill; Vice President of Scientific Affairs, Therapeutic Expertise, Oncology, at PRA International; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems; Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Author and Editor Disclosure
Synonyms and related keywords:
extrapulmonary small cell cancer, EPSCC, small cell cancer, lung cancer, lung cancer diagnosis, lung cancer treatment, lung carcinoma, respiratory tract cancer, respiratory tract cancer treatment, respiratory tract cancer diagnosis, respiratory tract carcinoma, small cell lung cancer, SCLC, paraneoplastic syndrome, syndrome of inappropriate secretion of antidiuretic hormone, SIADH, hypercalcemia, Merkel cell carcinoma
Background
Small cell carcinomas (SCC) commonly arise in the respiratory tract; however, it is not uncommon for these cells to arise in nonpulmonary sites, as extrapulmonary small cell carcinoma (EPSCC). Small cell carcinoma is a distinct clinical and pathologic entity that arises from cells of the amine precursor uptake and decarboxylation (APUD) system. Extrapulmonary small cell carcinoma is estimated to account for approximately 1000 new cancer cases per year in the United States. This number, however, appears to be an underestimation. Most available literature on this condition exists in the form of case reports and retrospective series. The role of local and systemic therapies for extrapulmonary small cell carcinoma treatment is still not clearly defined. Most reports indicate chemotherapy sensitivity and response rates similar to those seen in small cell lung cancer with similar chemotherapeutic regimens. Surgery appears to play a more important role in the management of extrapulmonary small cell carcinoma compared to the role of surgery for small cell lung cancer.
Pathophysiology
Histologic criteria for diagnosis of extrapulmonary small cell carcinoma are same as those for pulmonary small cell carcinoma, that is appearance of uniform small cells with sparse cytoplasm, dense nuclei, and inconspicuous nucleoli.1 Since extrapulmonary small cell carcinoma has been reported from multiple sites, it is thought that the cell of origin is identical and derives from those originating in neural crest and then migrating to different epithelial sites within the body. These cells are characterized by presence of intracytoplasmic neurosecretory granules and stain positively with chromogranin. Extrapulmonary small cell carcinoma has been reported to arise in almost all body sites except the central nervous system.2, 3 Primary sites may include esophagus, salivary glands, gastrointestinal tract (including small intestine and large intestine), pancreas, larynx, cervix uteri, uterus, urinary bladder, prostate, breast, and lacrimal gland in addition to skin, where it is also referred to as Merkel cell carcinoma.4 Like pulmonary small cell carcinoma (lung cancer), small cell carcinomas arising from extrapulmonary sites may be associated with paraneoplastic syndromes, notably syndrome of inappropriate secretion of antidiuretic hormone (SIADH) and hypercalcemia. However, deletions of chromosome arm 3p and c-myc amplification described in small cell pulmonary carcinoma have not been reported in extrapulmonary sites.
Frequency
United States
Approximately 1000 cases of extrapulmonary small cell carcinoma are reported annually, with an overall incidence of 0.1-0.4% of all cancers.
International
Global incidence of extrapulmonary small cell carcinoma is unknown.
Mortality/Morbidity
Because most of the literature is retrospective and in the form of case reports, estimating mortality rates is difficult. In addition, not all reported cases are managed uniformly, thereby making it further difficult to estimate prognosis. Long-term survival is, however, reported, especially in those treated with an aggressive multimodality approach. Extrapulmonary small cell carcinoma may have a similar prognosis to that of small cell lung cancer. Those presenting with disseminated disease have a very poor prognosis and short survival time despite management with chemotherapy, radiation therapy, or both. Long-term survival is reported in those presenting with localized disease.
Age
No predilection for race or sex is clear in the reported literature. However, most of these malignancies develop after the sixth decade of life.
History
Extrapulmonary small cell carcinoma is an aggressive neoplasm that enlarges rapidly and disseminates early in the course of illness. Due to multiplicity of sites where it can arise, there are no symptoms or signs specifically attributable to extrapulmonary small cell carcinoma. Patients may present with constitutional symptoms of fatigue, weakness, fever, weight loss, and night sweats. They may also have symptoms referable to the organ of origin, for instance hematuria in cases of bladder tumor, abdominal pain with or without obstruction with small or large bowel involvement, or hoarseness with laryngeal involvement.
Physical
Physical findings are again limited by the organ system involved and may include prostatic enlargement, skin nodules in case of Merkel cell carcinoma, or enlargement of regional draining lymph nodes. As with pulmonary small cell carcinoma, paraneoplastic syndromes have been described with extrapulmonary small cell carcinoma. Most common of these are hypercalcemia, syndrome of inappropriate secretion of antidiuretic hormone, and secretion of adrenocorticotropic hormone, and patients may present with symptoms and signs of excess calcium, hyponatremia, or corticosteroid excess depending upon the severity and rate of development of endocrine abnormality.
Causes
Etiology of extrapulmonary small cell carcinoma is unknown. While some authors have reported an association with tobacco smoking, others have not found a strong causative correlation with tobacco.
Other Problems to Be Considered
Metastatic neuroendocrine carcinoma
Pathologically, extrapulmonary small cell carcinoma needs to be differentiated from other tumors composed of small round blue cells under light microscopy including the following: - Lymphoma
- Rhabdomyosarcoma
- Carcinoids
Lab Studies
No laboratory investigations aid in the diagnosis of extrapulmonary small cell carcinoma. Most of the laboratory studies done in the workup are to assess end organ function prior to instituting therapy, especially chemotherapy, or to diagnose a suspected paraneoplastic syndrome.
- Complete blood count with differential is obtained to assess bone marrow reserve, but it may give clues to bone marrow infiltration by the tumor. Bone marrow infiltration is suspected based on a leukoerythroblastic (presence of red and white blood cell precursors in peripheral blood) picture of peripheral blood.
- Blood urea nitrogen and serum creatinine and electrolytes are obtained to asses renal function prior to instituting potentially nephrotoxic drugs as well as estimate renal clearance of chemotherapeutic agents. In addition, low sodium and abnormalities in other electrolytes such as potassium may point towards presence of a paraneoplastic syndrome.
- Serum bilirubin and transaminases are obtained to assess liver function and for appropriate dosing of hepatically cleared chemotherapeutic agents.
- Serum calcium is assessed for suspected hypercalcemia and bone metastases.
Imaging Studies
The diagnosis of extrapulmonary small cell carcinoma by definition requires a chest radiograph, computed tomographic scan, or both without findings of chest involvement. - Chest radiograph is obtained to exclude pulmonary involvement.
- CT scan of chest, abdomen, and pelvis is obtained to exclude pulmonary involvement and stage the extent of disease.
Procedures
- Bone marrow aspiration and biopsy are performed to confirm or rule out bone marrow involvement in case of peripheral blood abnormalities. Some authors recommend that bone marrow biopsy should be done in every patient to confirm limited disease.
- Sputum cytology, bronchoscopy, or both are performed to exclude pulmonary origin of small cell carcinoma.
- Special tests may be performed depending on primary site of origin:
- Upper endoscopy: Esophagus
- Direct laryngoscopy, bronchoscopy, and upper endoscopy: Origin in head and neck region
- Cystoscopy: Urinary bladder
- Lower endoscopy: Rectum and large bowel
- Pelvic examination: Cervix and uterus
Histologic Findings
Extrapulmonary small cell carcinoma histologically consists of sheets of uniform small round cells with scant cytoplasm, dense nuclei, and indistinct nucleoli. Immunohistochemical stains with silver impregnated stains usually have positive results.
Staging
There is no American Joint Committee on Cancer (AJCC) staging classification for extrapulmonary small cell carcinoma. In the reported literature, extrapulmonary small cell carcinoma is universally staged similarly to small cell carcinoma of lung, that is limited stage and extensive stage.
- Limited stage: Tumor is confined to organ of origin with or without regional lymph node involvement. Alternatively, limited stage has also been defined as that encompassed within one radiation port.
- Extensive stage: Disease has spread to distant organs or beyond regional lymph nodes.
Medical Care
No randomized studies exist to guide decisions regarding management of extrapulmonary small cell carcinoma. The organ and site of involvement, as well as extent of disease, are important in management. Based on experience published in the form of retrospective reviews, combination chemotherapy appears to form the mainstay of treatment, similar to that for small cell carcinoma of lung.5 Combination chemotherapy with a platinum-based combination has produced response rates similar to those seen in small cell lung cancer, and long-term survival has been reported.6
Patients with extrapulmonary small cell carcinoma and extensive stage disease should be treated initially with combination chemotherapy. The role of surgery and radiation therapy in this situation is not defined, but surgery may be used for palliative purposes. Those who achieve complete remission may have prolonged survival despite presenting with advanced-stage disease. Survival in excess of 120 months has been reported.
The optimum therapy for limited-stage extrapulmonary small cell carcinoma is less clearly defined, but the principals of management of limited stage small cell carcinoma have been frequently applied in the management of limited stage extrapulmonary small cell carcinoma. Surgery, radiation, and chemotherapy may play a role in the management. Unlike small cell lung cancer, surgery is often the primary therapy in such individuals since the presentation in organs such as esophagus, thyroid, and female genitourinary tract may lead to initial surgical resection. In some of these patients, initial surgical resection may result in complete removal of malignancy. However, due to propensity for systemic spread, all such patients should be considered for combination chemotherapy after surgical resection.
The role of radiation therapy is not clear; however, prolonged survival has been reported in limited numbers of patients after radiation therapy alone when presenting at a very limited stage.
Patients with extrapulmonary small cell carcinoma who present with localized disease may be treated with chemotherapy and local therapy in the form of surgery or radiation therapy. Those presenting with extensive stage disease are best treated with combination chemotherapy. The active regimens include those containing platinum (cisplatin or carboplatin) or anthracyclines.
Surgical Care
See Medical Care.
Consultations
The care of patients with limited extrapulmonary small cell carcinoma should involve a multidisciplinary approach that includes initial consultations with surgical, medical, and radiation oncologists to devise the most appropriate management plan.
Medication used in the management of extrapulmonary small cell carcinoma includes chemotherapeutic agents to effect tumor shrinkage and induce remission as well as medication to reduce morbidity from treatment, malignancy, or both.
Drug Category: Antiemetic agents
Nausea and vomiting caused by antineoplastic agents is induced by stimulation of chemoreceptor trigger zone. This effect is mediated by central neurotransmitters (ie, dopamine and acetylcholine). The severity of nausea and vomiting caused by antineoplastic agents varies with the agent or combination used, but it may be so disabling that patients occasionally decline continuation of chemotherapy. Appropriate prophylaxis and treatment of nausea and vomiting are therefore critical for administration of chemotherapy.
| Drug Name | Metoclopramide (Clopra, Reglan, Maxolon, Octamide PFS) |
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| Description | Metoclopramide has central and peripheral antiemetic activity. In the CNS it acts on the chemoreceptor trigger zone while in the GI tract it stimulates acetylcholine release in the myenteric plexus. |
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| Adult Dose | 5-10 mg PO or 5-20 mg IV/IM tid |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; pheochromocytoma; GI hemorrhage, obstruction, or perforation; history of seizure disorders |
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| Interactions | Opioid analgesics may increase toxicity in CNS; may cause additive effects with other drugs that cause extrapyramidal reactions; MAOIs, tricyclic antidepressants, or sympathomimetics may cause hypertension; may increase serum levels of cyclosporine, sirolimus, or tacrolimus; may decrease digoxin serum levels |
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| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
|
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| Precautions | Caution in breastfeeding women, depression, hypertension, Parkinson disease, and conditions aggravated by anticholinergic or antidopaminergic effects; may cause tardive dyskinesia |
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| Drug Name | Dexamethasone (Decadron) |
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| Description | Dexamethasone is a synthetic corticosteroid commonly used in combination with serotonin receptor antagonists or metoclopramide in prevention and treatment of chemotherapy-induced nausea and vomiting. |
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| Adult Dose | 8-20 mg PO/IV 30 min prior to chemotherapy combined with 5-HT3-receptor antagonist |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; active infection |
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| Interactions | Induces CYP-450 3A4, and coadministration of other CYP-450 3A4 enzyme inducers (ie, barbiturates, phenytoin, rifampin) decreases effects; decreases effects of salicylates and vaccines used for immunization; may antagonize effects of neuromuscular blockers |
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| Pregnancy | C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
|
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| Precautions | Increases risk of multiple complications, including severe infections; monitor adrenal function when tapering drug; abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections are possible complications; if mother exposed to substantial doses of corticosteroids during pregnancy, monitor infant for hypoadrenalism |
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| Drug Name | Ondansetron (Zofran) |
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| Description | Selective 5-HT3-receptor antagonist. Unclear whether effect is centrally and/or peripherally mediated. Used to prevent chemotherapy-induced nausea and vomiting. |
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| Adult Dose | 8 mg PO 30 min before chemotherapy; repeat once following 8 h, then bid/tid for 1-2 d after completion of chemotherapy; dosage in elderly population is same
32 mg IV infused over 15 min 30 min before chemotherapy; alternatively, 0.15 mg/kg IV 30 min before chemotherapy, repeat q4h for 2 doses
Not to exceed 8 mg/d in severe liver disease |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Although potential for cytochrome P-450 inducers (eg, barbiturates, rifampin, carbamazepine, phenytoin) to change half-life and clearance, dosage adjustment usually not required |
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| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
|
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| Precautions | Administer for prevention of nausea and vomiting, not for rescue of nausea and vomiting; headache occurs commonly (up to 40% of patients) |
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| Drug Name | Granisetron (Kytril) |
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| Description | Selective 5-HT3-receptor antagonist. Unclear whether effect is centrally and/or peripherally mediated. Used to prevent chemotherapy-induced nausea and vomiting. |
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| Adult Dose | 1-2 mg PO as single dose within 1 h before chemotherapy; no dose adjustment for elderly persons
10 mcg/kg IV 30 min before chemotherapy, usual dose 700-1000 mcg IV |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity |
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| Interactions | None reported |
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| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
|
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| Precautions | To be administered for prevention of nausea and vomiting, not for rescue of nausea and vomiting; caution in liver disease |
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| Drug Name | Dolasetron (Anzemet) |
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| Description | Binds to 5-HT3 receptors located on vagal neurons in GI tract, blocking signal to VC, thus preventing nausea and vomiting. |
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| Adult Dose | 100 mg/dose PO as single dose within 1 h before chemotherapy; no dose adjustment for elderly persons
1.8 mg/kg IV 30 min before chemotherapy; not to exceed 100 mg/dose; alternatively 100 mg IV 30 min before chemotherapy |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity |
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| Interactions | Although potential for CYP-450 inducers (eg, barbiturates, rifampin, carbamazepine, phenytoin) to decrease half-life and increase clearance, dosage adjustment usually not required; CYP-450 3A4 inhibitors (eg, itraconazole, erythromycin, ritonavir) may decrease clearance; coadministration with drugs prolonging QT interval (eg, sotalol, amiodarone) may exacerbate cardiotoxicity |
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| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
|
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| Precautions | To be administered for prevention of nausea and vomiting, not for rescue of nausea and vomiting; may prolong QT interval, mildly elevates LFTs |
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| Drug Name | Palonosetron (Aloxi) |
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| Description | Selective 5-HT3 receptor antagonist with long half-life (40 h). Indicated for prevention and treatment of chemotherapy-induced nausea and vomiting. Blocks 5-HT3 receptors peripherally and centrally in chemoreceptor trigger zone. |
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| Adult Dose | 0.25 mg IV once (30 min before chemotherapy); administer over 30 s; do not repeat dose within 7 d |
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| Pediatric Dose | <18 years: Not established |
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| Contraindications | Documented hypersensitivity |
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| Interactions | None reported |
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| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
|
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| Precautions | May cause headache, constipation, diarrhea, or dizziness |
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Drug Category: Antineoplastic agents
Chemotherapy forms the mainstay of management of extrapulmonary small cell carcinoma. Antineoplastic agents are used in potentially curative therapy in limited extrapulmonary small cell carcinoma in combination with radiation therapy, surgery, or both. In extensive extrapulmonary small cell carcinoma, chemotherapy is used for prolongation of survival or palliation of symptoms. Antineoplastic agents interfere with cell division and growth. Some antineoplastic agents are cell-cycle dependent and phase specific, like antimetabolites (cytosine arabinoside, methotrexate), while others, like alkylating agents (cyclophosphamide), are not.
| Drug Name | Etoposide (Toposar, VePesid) |
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| Description | Inhibits topoisomerase II enzyme leading to breakage of DNA strands. Etoposide is cell cycle specific and causes cell cycle arrest in late S and early G2 phase of cell cycle. |
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| Adult Dose | PE regimen: 100 mg/m2 IV days 1-3 of cycle, repeat every 3-4 wk for 4-6 cycles
CAVE regimen: 100 mg/m2 IV day 1 of cycle, repeat every 3-4 wk for 4-6 cycles
PEC regimen: alternate 50 mg/d and 100 mg/d PO on days 1-10 of cycle, repeat every 3-4 wk for 4-6 cycles
Single-agent regimen: 50 mg PO bid for days 1-14 of cycles, repeat cycle every 3-4 wk for 4-6 cycles
Adjust dose in hepatic or renal dysfunction
Total bilirubin (TB) 1.5-3 mg/dL: 50% dose reduction
TB 3.1-4.9 mg/dL: 75% dose reduction
TB >5: Avoid use
CrCl 15-50 mL/min: 25% dose reduction
|
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; IT administration (may cause death) |
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| Interactions | May prolong effects of warfarin and increase clearance of methotrexate; cyclosporine has additive effects in cytotoxicity of tumor cells; high dose of cyclosporine (serum concentration >2000 ng/mL) decreases clearance, leading to increased risk of neutropenia; zidovudine increases serum concentration, resulting in increased toxicity |
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| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
|
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| Precautions | Bleeding, severe myelosuppression, nausea, vomiting, hypotension, allergic reaction, and alopecia may occur; reduce dose in hepatic (eg, increased TB) or renal (eg, decreased CrCl) impairment |
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| Drug Name | Cisplatin (Platinol) |
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| Description | Alkylating agent causing intrastrand and interstrand cross-linking of DNA, leading to strand breakage. Has broad range of antitumor activity. Use in testicular, ovarian, and transitional cell carcinomas. |
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| Adult Dose | PE (cisplatin-etoposide) regimen: 25 mg/m2 IV days 1-3 of cycle, repeat every 3-4 wk for 4-6 cycles (or 100 mg/m2 IV day 1) |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; preexisting renal insufficiency; myelosuppression; hearing impairment |
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| Interactions | Increases toxicity of bleomycin and ethacrynic acid; other nephrotoxic drugs (eg, aminoglycosides, amphotericin B, cyclosporine) increase nephrotoxicity; bleomycin, cytarabine, methotrexate, and ifosfamide may accumulate owing to decreased renal excretion; may worsen cytotoxicity of etoposide; mesna and sodium thiosulfate directly inactivate cisplatin; dipyridamole increases cytotoxicity by enhancing cellular uptake; paclitaxel-related peripheral neuropathy may be increased in patients previously treated with cisplatin |
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| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
|
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| Precautions | Administer adequate hydration before and for 24 h after cisplatin dosing to reduce risk of nephrotoxicity; myelosuppression, ototoxicity, nausea, and vomiting may occur; peripheral blood cell counts and serum electrolyte levels should be monitored; requires close monitoring of pretreatment creatinine level and CrCl and posttreatment magnesium levels; neurologic examination should be performed regularly; major dose-limiting toxic effect is peripheral neuropathy; can cause acute or chronic renal failure in up to one third of patients treated but this can usually be prevented by vigorous hydration and saline diuresis; renal tubular wasting of potassium and magnesium is common (monitor closely); cellulitis and fibrosis have rarely occurred after extravasation; avoid aluminum needles |
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| Drug Name | Carboplatin (Paraplatin) |
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| Description | Analog of cisplatin (ie, platinum-salt alkylating agent). Has similar efficacy as cisplatin but with lower toxicity profile. Carboplatin is associated with less renal toxicity but enhanced myelosuppression compared to cisplatin. Mechanism of action for carboplatin is production of cross-links within and between strands of DNA. |
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| Adult Dose | Dose based on following formula:
Total dose (mg) = (target AUC) X (GFR+25); where AUC expressed in mg/mL/min and GFR expressed in mL/min
Total dose (mg) = 6 mg/mL/min X (GFR + 25) IV on day 1 of cycle, repeat every 3-4 wk for 4-6 cycles |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; bone marrow suppression |
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| Interactions | Nephrotoxicity and ototoxicity increase with aminoglycosides and other nephrotoxic drugs |
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| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
|
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| Precautions | Monitor bone marrow function; do not use needles containing aluminum (forms precipitant); caution in renal impairment (adjust dose); elderly or those previously treated with cisplatin at risk of peripheral neuropathy; high doses associated with vision loss |
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| Drug Name | Cyclophosphamide (Cytoxan, Neosar) |
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| Description | Chemically related to nitrogen mustards. As alkylating agent, mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells. |
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| Adult Dose | CAV or CAVE regimens: 1000 mg/m2 IV on day 1 of cycle, repeat every 3-4 wk for 4-6 cycles |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; severely depressed bone marrow function |
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| Interactions | Fatal cardiotoxicity reported with coadministration of pentostatin
Allopurinol may increase risk of bleeding or infection and exacerbate myelosuppressive effects; may potentiate anthracycline-induced cardiotoxicity; may reduce digoxin (tab) serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; CYP-450 enzyme inducers (eg, phenobarbital, phenytoin, rifampin, carbamazepine) may increase rate of cyclophosphamide metabolism; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity; ondansetron may decrease serum levels and half-life |
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| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
|
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| Precautions | Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis |
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| Drug Name | Doxorubicin (Adriamycin, Rubex) |
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| Description | Inhibits topoisomerase II and produces free radicals, which may cause destruction of DNA. The combination of these 2 events can in turn inhibit growth of neoplastic cells. |
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| Adult Dose | CAV or CAVE regimens: 50 mg/m2 IV on day 1 of cycle, repeat every 3-4 wk for 4-6 cycles |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; severe heart failure; cardiomyopathy; impaired cardiac function; completed cumulative doses of anthracyclines or anthracenes; preexisting myelosuppression |
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| Interactions | May decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity; cyclophosphamide increases cardiac toxicity |
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| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
|
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| Precautions | Irreversible cardiac toxicity and myelosuppression may occur; extravasation may result in severe local tissue necrosis; reduce dose with impaired hepatic function |
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| Drug Name | Vincristine (Oncovin) |
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| Description | Inhibits tubulin polymerization during mitosis. G2 phase specific. |
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| Adult Dose | CAV or CAVE regimens: 1.4 mg/m2 IV push; not to exceed 2 mg/dose on day 1 of cycle, repeat every 3-4 wk for 4-6 cycles |
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| Pediatric Dose | Not established |
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| Contraindications | Documented hypersensitivity; IT administration (may be fatal |
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| Interactions | Mitomycin-C may cause acute pulmonary reaction; asparaginase, colony-stimulating factors (eg, sargramostim, filgrastim), or nifedipine increases toxicity; CYP-450 3A4 inducers (ie, carbamazepine, phenytoin, phenobarbital, rifampin) may increase clearance; CYP-450 3A4 inhibitors (ie, itraconazole, quinupristin/dalfopristin, sertraline, ritonavir) may decrease clearance |
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| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
|
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| Precautions | Caution in severe cardiopulmonary impairment, hepatic impairment (decrease dose), or preexisting neuromuscular disease |
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Further Outpatient Care
- Patients with extrapulmonary small cell carcinoma require close monitoring for adverse effects of chemotherapy. Complete blood counts with differential counts should be checked prior to each cycle of chemotherapy to ensure adequate hematologic recovery. Liver and renal function should be monitored to detect toxicity from chemotherapy as well as to assess if adjustment of chemotherapy doses is needed.
- Response to therapy is monitored by obtaining CT scans after 2 cycles of chemotherapy before chemotherapy is continued.
- If elevated prior to therapy, serum lactate dehydrogenase is a good marker and should be monitored.
Deterrence/Prevention
Data linking extrapulmonary small cell carcinoma to tobacco smoking are inconclusive; however, at least one study has reported that most patients with extrapulmonary small cell carcinoma in the study were former or current smokers. Since smoking is implicated as an etiologic agent in several different kinds of malignancies, smoking cessation education and programs with a concerted efforts form health care providers and government agencies are needed.
Complications
Tumor lysis syndrome: Tumor lysis can occur rapidly in patients with small cell carcinomas on institution of therapy.
Prognosis
See Mortality/Morbidity.
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Extrapulmonary Small Cell Carcinoma excerpt Article Last Updated: Oct 14, 2008
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