eMedicine Specialties > Pediatrics: General Medicine > Oncology
Adrenal Carcinoma: Treatment & Medication
Updated: Nov 26, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Medical care in patients with adrenal carcinomas is supportive or adjuvant to surgical resection.
- Chemotherapy is as follows:
- When metastatic disease cannot be removed or when biochemical evidence of tumor secretion persists after surgical removal, chemotherapy is often considered. At present, no data suggest that chemotherapy can fulfill a truly adjuvant role that improves patient survival and prevents relapse after incomplete or total resection.
- Anecdotal data suggest that at least 2 drugs have single-agent activity that may prolong survival. If these drugs are thoroughly studied, they may ultimately demonstrate the possibility of having an adjuvant role. The 2 drugs are mitotane (trivial name, o,p’-DDD; trade name, Lysodren) and cisplatin (trivial name, CDDP; trade name, Platinol). Researchers have long known that mitotane dramatically decreases the production of adrenocortical hormone and ultimately ablates the adrenal cortex. As a single agent, cisplatin can shrink metastatic disease. In recent studies, etoposide and doxorubicin were added to cisplatin and mitotane.
- Mitotane and cisplatin are most commonly used for palliation. Mitotane is used to decrease residual cortical hormonal production, and cisplatin is used to shrink metastases in the lung and elsewhere to prolong survival after the disease becomes unresectable.
- Small studies have been conducted to examine etoposide and platinum or etoposide, doxorubicin, and platinum for adjuvant use.
- Although no program of conventional chemotherapy appears curative in metastatic adrenal carcinoma, prolonged survival has been seen with the use of mitotane and other chemotherapy drugs and surgery.2
- Radiation therapy may be helpful in the palliation of unresectable disease that is unresponsive to medical therapy.
- An anecdotal case of successful autologous transplantation, chemotherapy, and surgically reduced disease in a young child was reported, with 2-year follow up.3
Surgical Care
- Treatment of adrenocortical carcinoma begins with surgical care. Surgery is the mainstay of treatment and currently appears to be the major hope for cure. Every reasonable attempt should be made to render the patient disease-free at the primary site, at sites of local invasion, and at sites of metastatic disease.
- In the author’s experience, aggressive surgical care led to survival for longer than 10 years in 2 patients, one of whom was concurrently treated with medical therapy. This patient had a large, bulky tumor with no local invasion; the other patient had a stage II tumor and underwent several follow-up thoracotomy procedures.
- Case reports indicate that repeated thoracotomy can allow for more than 10 years of high-quality survival despite recurring crops of metastatic disease. In a study at Memorial Sloan-Kettering Cancer center, investigators evaluated patients with adrenocortical carcinoma.4 Aggressive primary surgical removal and aggressive surgical treatment of local or distant relapse led to long-term survival rates far superior to reported in previous studies, regardless of the patients' ages. One important feature of this study was that patients who underwent a complete second resection had a median survival of 74 months (5-y survival rate, 57%). The current role of surgical resection in the treatment of adrenocortical carcinoma cannot be overemphasized.
- Patients with symptoms of hormone overproduction and biochemical evidence of adrenocortical hormone overproduction should be supported in the postoperative period after major resection. These patients have suppressed endogenous adrenocortical hormone production. Stress doses of hydrocortisone that ultimately lead to maintenance doses and tapering (should the patient not be given further therapy) are indicated.
Consultations
- Optimal care of pediatric patients with adrenocortical carcinoma includes consultation with a pediatric surgeon who has extensive experience in cancer surgery and consultation with a pediatric oncologist who may have managed cases of adrenocortical carcinoma.
Medication
Adjuvant or palliative treatment has been studied by using mitotane, cisplatin, etoposide, and doxorubicin. Mitotane leads to autodestruction of the adrenal cortex. Therefore, it is used in almost all protocols in the hope that it will decrease any autonomous hormone production and suppress tumor growth. Chemotherapy has focused on 3 antineoplastics given alone or in combination: cisplatin, etoposide, and doxorubicin. Studies have focused on etoposide and cisplatin or etoposide, doxorubicin, and cisplatin.
Antineoplastic agents
Cancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect this growth. After cells divide, they enter a period of growth (phase G1), followed by DNA synthesis (phase S). The next phase is a premitotic phase (phase G2). Finally, a period of mitotic cell division (phase M) occurs.
Rates of cell division vary for different tumors. Most common cancers grow slowly compared with normal tissues, and the rate may decrease if tumors are large. This difference allows healthy cells to recover from chemotherapy more quickly than do malignant cells, and this is the rationale for current cyclic dosage schedules.
Antineoplastic agents interfere with cell reproduction. Some agents are specific to certain phases of the cell cycle, whereas others (eg, alkylating agents, anthracyclines, cisplatin) are not phase specific. Cellular apoptosis (ie, programmed cell death) is another potential mechanism of many antineoplastic agents.
Mitotane (Lysodren)
Decreases production of cortisol by causing adrenal atrophy and affecting mitochondria in adrenocortical cells. No pediatric standards or dosages established, and doses in children must be individualized.
Adult
Pediatric
500 mg PO qid initially; may increase to 10 g/m2/d
CNS depressants may increase toxicity; may increase metabolism of warfarin, decreasing levels; spironolactone may decrease effects
Documented hypersensitivity
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
Precautions
GI toxicity (eg, anorexia, nausea, vomiting, diarrhea), neurotoxicity (eg, lethargy, somnolence, dizziness, vertigo, depression), or dermatologic toxicity (eg, evanescent papular erythematous rash) may limit dose escalation; dose escalation may precede toxicity; blood levels of mitotane associated with response as opposed to PO dose; clinical response may not occur for up to 3 mo at maximum tolerated dose; exogenous administration of adrenocortical hormones (hydrocortisone and/or fludrocortisone) required
Cisplatin (Platinol)
Inhibits DNA synthesis and, therefore, cell proliferation by causing DNA crosslinking and denaturation of double helix.
Adult
Pediatric
<10 kg: 2.5-3.3 mg/kg IV q3wk
>10 kg: 75-100 mg/m2 IV q3wk
Increases toxicity of bleomycin and ethacrynic acid
Documented hypersensitivity; preexisting renal insufficiency; myelosuppression; hearing impairment
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Administer only under care of experienced pediatric oncologist using conventional procedures to prevent ototoxicity and nephrotoxicity; in addition to usual monitoring with intensive chemotherapy, observe and treat renal tubular defects, renal loss of electrolytes (eg, magnesium, potassium), renal insufficiency, ototoxicity, myelosuppression, and neurotoxicity; adequately hydrate before and 24 h after dosing to reduce risk of nephrotoxicity
Doxorubicin (Adriamycin)
Cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var. caesius. Blocks DNA and RNA synthesis by inserting between adjacent base pairs and binding to sugar-phosphate backbone of DNA, inhibiting DNA polymerase. Binds to nucleic acids presumably by specific intercalation of anthracycline nucleus with DNA double helix. Can also cause DNA strand breakage because of effects on topoisomerase II.
Powerful iron chelator. Iron-doxorubicin complex induces production of free radicals that can destroy DNA and cancer cells.
Maximum toxicity during S phase of cell cycle.
Has multiphasic disappearance curve, with half-lives up to 30 h. Does not cross blood-brain barrier but taken up rapidly by heart, lungs, liver, kidney, and spleen.
Both mutagenic and carcinogenic. Dosage related to body surface area.
Antiproliferative drugs may be useful for patients with diffuse metastases to palliate symptoms.
Liposomes in different drug products can vary in chemical and physical properties, which can substantially affect functional properties.
Adult
Pediatric
<10 kg: 0.6-1.5 mg/kg IV q3wk
>10 kg: 20-45 mg/m2 IV q3wk
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
Documented hypersensitivity; severe heart failure, cardiomyopathy, impaired cardiac function, preexisting myelosuppression; previous complete cumulative doses of doxorubicin, daunorubicin, idarubicin, or other anthracyclines and anthracenes
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Irreversible cardiac toxicity and myelosuppression may occur; extravasation may result in severe local tissue necrosis; reduce dose in patients with impaired hepatic function
Etoposide (Toposar, VePesid)
Glycosidic derivative of podophyllotoxin that exerts cytotoxic effect by stabilizing normally transient covalent intermediates formed between DNA substrate and topoisomerase II. Leads to single-strand and double-strand DNA breaks that arrest cellular proliferation in late S or early G2 phase of cell cycle.
Adult
Pediatric
<10 kg: 3.3 mg/kg/d IV for 3 d q3wk
>10 kg: 100 mg/m2/d IV for 3 d q3wk
May prolong effects of warfarin and increase clearance of methotrexate; cyclosporine and etoposide have additive effects in cytotoxicity of tumor cells
Documented hypersensitivity; clinically significant hypotension
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
IT administration may cause death; bleeding and severe myelosuppression; withhold or suspend therapy if platelet count <50,000 or if absolute neutrophil count <500/μL; reduce dose by 20% if patient has granulocytic fever or had previous radiation therapy; reduce dose in hepatic impairment (increased total bilirubin) or renal impairment (decreased creatinine clearance)
More on Adrenal Carcinoma |
| Overview: Adrenal Carcinoma |
| Differential Diagnoses & Workup: Adrenal Carcinoma |
 Treatment & Medication: Adrenal Carcinoma |
| Follow-up: Adrenal Carcinoma |
| References |
| « Previous Page | Next Page » |
References
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Further Reading
Keywords
adrenal carcinoma, adrenal cortical carcinoma, adrenocortical carcinoma, adrenal cancer, abdominal mass, adrenal hormone hypersecretion, Li-Fraumeni complex, Cushingoid features, virilization, androgen production, premature puberty, premature pubic hair, acne, tumor, cancer, P53 gene, Beckwith-Wiedemann syndrome, Carney complex, multiple endocrine neoplasia 1, hemihypertrophy syndrome, hypertension, obesity, gynecomastia, precocious sexual development, neuroblastoma, Wilms tumor
