eMedicine Specialties > Oncology > Carcinomas of the Lung and Other Intrathoracic Carcinomas
Lung Cancer, Oat Cell (Small Cell): Treatment & Medication
Updated: May 22, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Small cell lung cancer (SCLC) differs from other lung cancer types because of its rapid growth and propensity for early dissemination. Surgery plays little, if any, role in the management of small cell lung cancer, except in a small minority of patients who present with very early stage disease confined to lung parenchyma.
Patients with limited stage disease with apparent clinical stage T1/T2, N0 should undergo mediastinoscopy. Should the mediastinoscopy prove to be negative, they might have a surgical resection to involve lobectomy, wedge resection, or pneumonectomy together with mediastinal lymph node removal.1 If mediastinal lymph node involvement is not found, then consideration should be given to a 4-6 cycle course of adjuvant chemotherapy with combinations of agents known to be effective in limited or extensive disease, that is etoposide and either cisplatin or carboplatin. This would be a reasonable recommendation despite the relative lack of evidence-based data to support it because of the aggressive nature of small cell lung cancer and its known tendency to metastasize early and often.
Management of limited-stage small cell lung cancer involves combination chemotherapy, usually with a platinum-containing regimen, and thoracic radiation therapy. If the patient achieves a complete remission, he or she would be offered prophylactic cranial irradiation.
Extensive-stage small cell lung cancer remains incurable with current management options, and patients are treated with combination chemotherapy. Several chemotherapy combinations are active in small cell lung cancer, but usually a platinum-containing regimen is chosen. It should be noted, however, that despite great enthusiasm of 2 decades ago, little change in survival has been shown for both limited- and extensive-stage small cell lung cancer. Very few new agents with activity in small cell lung cancer have been identified. While identification of molecular targets and targeted therapies has proceeded at a brisk pace in non-small-cell lung cancer, the same has not been true for small cell lung cancer. Treatment strategies involving angiogenesis blocking agents are currently being tested.
Table 2. Commonly Used Chemotherapy Regimens in Small Cell Lung Cancer
Open table in new window
Table
| Regimen | Dose |
| CAV | |
| Cyclophosphamide | 1000 mg/m2 IV day 1 |
| Doxorubicin (Adriamycin) | 50 mg/m2 IV day 1 |
| Vincristine | 2 mg IV |
| PE | |
| Cisplatin | 25 mg/m2 IV days 1-3 |
| Etoposide | 100 mg/m2 IV days 1-3 |
| CAVE | |
| Cyclophosphamide | 1000 mg/m2 IV day 1 |
| Doxorubicin (Adriamycin) | 50 mg/m2 IV day 1 |
| Vincristine | 1.4 mg/m2 IV day 1 (maximum 2 mg) |
| Etoposide | 100 mg/m2 IV day 1 |
| PEC | |
| Paclitaxel | 200 mg/m2 IV day 1 |
| Etoposide | 50 mg/d PO alternating with 100 mg/d PO from days 1-10 |
| Carboplatin | AUC 6 IV day 1 |
| Topotecan | 1.5 mg/m2 IV day 1-5 |
| Etoposide | 50 mg PO bid days 1-14 |
| Regimen | Dose |
| CAV | |
| Cyclophosphamide | 1000 mg/m2 IV day 1 |
| Doxorubicin (Adriamycin) | 50 mg/m2 IV day 1 |
| Vincristine | 2 mg IV |
| PE | |
| Cisplatin | 25 mg/m2 IV days 1-3 |
| Etoposide | 100 mg/m2 IV days 1-3 |
| CAVE | |
| Cyclophosphamide | 1000 mg/m2 IV day 1 |
| Doxorubicin (Adriamycin) | 50 mg/m2 IV day 1 |
| Vincristine | 1.4 mg/m2 IV day 1 (maximum 2 mg) |
| Etoposide | 100 mg/m2 IV day 1 |
| PEC | |
| Paclitaxel | 200 mg/m2 IV day 1 |
| Etoposide | 50 mg/d PO alternating with 100 mg/d PO from days 1-10 |
| Carboplatin | AUC 6 IV day 1 |
| Topotecan | 1.5 mg/m2 IV day 1-5 |
| Etoposide | 50 mg PO bid days 1-14 |
Treatment recommendations can be summarized as follows:
- Single-agent chemotherapy: Several chemotherapeutic agents have been identified in the last 3 decades that yield response rates in excess of 30% in previously untreated patients who have small cell lung cancer. Even though cisplatin is currently the most widely used agent in combination chemotherapy programs, response rate data for single-agent cisplatin in previously untreated patients with small cell lung cancer are lacking. In previously treated patients, however, cisplatin has shown a response rate of 17%.
- Currently cisplatin, etoposide, vincristine, doxorubicin, and cyclophosphamide are the agents most commonly employed to treat previously untreated patients with small cell lung cancer. Scheduling of etoposide has been demonstrated to be important in achieving a higher response rate, and currently etoposide is given over 3 days.
- Protracted oral administration of etoposide has been an acceptable initial therapy in elderly patients with extensive-stage small cell lung cancer, especially in those with poor performance status, but more recent studies suggest combination chemotherapy may be better than single-agent oral etoposide in those with good performance status.
- The taxanes and topotecan have emerged as active agents in previously untreated patients with small cell lung cancer. The response rates range from approximately 40% with topotecan to 50% with paclitaxel.
- Combination chemotherapy: Even though a few studies have suggested that the response rates and survival may be comparable between single-agent etoposide and more standard combination chemotherapy regimens in previously untreated patients with small cell lung cancer, combination chemotherapy is accepted widely as being associated with superior response rates and survival. A number of randomized trials have tried to answer the questions of superiority of combination over single-agent chemotherapy, the number of drugs in combination, and dose intensity, and nonrandomized trials of combination chemotherapy have shown superior response rates and survival compared to single-agent chemotherapy.
- The combination of cisplatin and etoposide (PE) is currently the most widely used regimen in both limited- and extensive-stage small cell lung cancer.
- The combination of cyclophosphamide, doxorubicin (Adriamycin), and vincristine (CAV) has been compared to PE in at least 2 randomized trials of previously untreated extensive-stage small cell lung cancer showing similar survival outcomes.
- The combination of cisplatin and etoposide is associated with less myelosuppression, while CAV has the convenience of administration in a single day (PE requires a 3-day program).
- Dose intensity and density: Several trials have tested the use of higher doses of standard chemotherapeutic regimens in previously untreated small cell lung cancer. Despite early enthusiasm brought on by higher initial response rates, most of these trials have failed to improve survival.
- A trial reported by Arriagada et al comparing standard and higher doses of cyclophosphamide and cisplatin in the first cycle of chemotherapy only yielded a superior survival rate in patients receiving higher dose chemotherapy.4 Higher dose regimens, however, may cause life-threatening myelosuppression and, in the absence of survival advantage, should not be used outside a clinical trial.
- Another approach to increase the intensity of chemotherapy is to shorten the interval between cycles (increased dose density). Again, even though phase II trials suggested the superiority of such an approach, randomized trials failed to show an advantage of intensive weekly chemotherapy over standard regimens. One of the problems has been myelosuppression with weekly programs such that the planned dose intensity has not been reached. Growth factor support may overcome this, but until randomized trials are reported showing clear superiority of such an approach, it remains investigational.
- High-dose chemotherapy with bone marrow or stem cell transplantation: The available data do not support the use of such an approach because it has not yielded better survival rates than standard management and is associated with greater immediate and delayed toxicity.
- Standard management of limited-stage small cell lung cancer: Staging should be adequate. Any pleural effusion should be tested cytologically for malignant cells, and isolated liver or adrenal lesions should be sampled by fine-needle aspiration before a diagnosis of limited stage is made. Some authorities suggest a bone marrow examination in the absence of any other evidence of spread.
- Standard management involves combination chemotherapy with a cisplatin-containing regimen and concurrent thoracic radiotherapy. The chemotherapy cycles are repeated every 3 weeks, and currently no data support continuation of chemotherapy beyond 6 cycles. In North America, the chemotherapy regimen used is etoposide and cisplatin. (Should the patient relapse after 6 months of completion of induction therapy, an attempt may be made to repeat the induction regimen. Relapses prior to the 6 month point would require salvage therapy.)
- Patients are started on thoracic radiotherapy, which should be begun as early as possible according to some authorities. Others advocate giving the radiation therapy concomitantly with the fourth cycle of chemotherapy.
- A randomized trial reported by Takada and colleagues that compared cisplatin and etoposide with concurrent versus sequential thoracic radiotherapy reported superior 2- and 5-year survival rates (2-y survival 35.1% versus 54.4%, and 5-y survival 18.3% versus 23.7% in favor of concurrent chemotherapy and radiation) with concurrent approach. Hematologic toxicity was greater in concurrent arm.5
- Another randomized trial by Turrisi and colleagues demonstrated a slight superiority of concurrent hyperfractionated radiotherapy given with 4 cycles of PE in limited-stage small cell lung cancer. Five-year survival rates in this trial were 26% versus 16% in favor of hyperfractionated radiotherapy.6
- Prophylactic cranial irradiation: The use of prophylactic cranial irradiation (PCI) was initially considered controversial.7 Several randomized trials showed a decrease in CNS relapse rate with PCI but no survival advantage. Additionally, patients receiving PCI had a higher incidence of neuropsychiatric dysfunction than those who did not receive PCI. Arriagada et al reported a meta-analysis of randomized trials of PCI in limited-stage small cell lung cancer and showed a 5% overall survival advantage in those receiving PCI.4 Even though such an analysis has inherent limitations, PCI is currently offered to patients with limited-stage small cell lung cancer who have achieved complete remission after having completed the full chemoradiotherapy regimen. Such therapy decreases the incidence of later intracranial metastases and prolongs survival. It should be regarded as standard therapy.
- Standard management involves combination chemotherapy with a cisplatin-containing regimen and concurrent thoracic radiotherapy. The chemotherapy cycles are repeated every 3 weeks, and currently no data support continuation of chemotherapy beyond 6 cycles. In North America, the chemotherapy regimen used is etoposide and cisplatin. (Should the patient relapse after 6 months of completion of induction therapy, an attempt may be made to repeat the induction regimen. Relapses prior to the 6 month point would require salvage therapy.)
- Standard management of extensive-stage small cell lung cancer: Patients with extensive-stage disease are treated with combination chemotherapy alone. Even though a combination of cisplatin and etoposide remains most widely used, a recently reported randomized trial compared the combination of cisplatin with either etoposide or irinotecan in extensive-stage small cell lung cancer. The combination of cisplatin and irinotecan was found superior to that of cisplatin and etoposide, with a median survival of 12.8 months with the cisplatin/irinotecan combination versus 9.4 months with cisplatin and etoposide. The 2-year survival rate was also superior at 19.5% versus 5.2%.8,9
However, a confirmatory study in the United States failed to show superiority of either regimen. Possible reasons for these results may be different dose and schedule of chemotherapeutic agents as well as genetic changes within different study populations. Although etoposide/cisplatin and irinotecan/cisplatin had comparable overall response rates and survival outcomes, the combination irinotecan/cisplatin had more gastrointestinal toxicity.10
Etoposide/cisplatin remains the standard of care in North America for extensive small cell lung cancer. A recent clinical trial in Germany reported that topotecan/cisplatin had a similar overall response rate to etoposide/cisplatin in extensive small cell lung cancer but a better time to progression and objective response rate than did etoposide/cisplatin.11 A trial comparing the two regimens in North America has not yet been performed.- Radiation therapy is used only to palliate symptoms, if required (eg, for painful bone metastases). Response rates are excellent, but patients invariably relapse.
- Brain metastases at the time of initial diagnosis in extensive small cell lung cancer is present in about 18% of patients. This incidence increases to about 80% at 2 years. A recent study by the European Organization for Research and Treatment of Cancer (EORTC) randomized patients responding to systemic chemotherapy between prophylactic cranial radiation (PCI) versus no PCI. One-year survival for PCI group was 27.1% compared to 13.3% for those without PCI. Prophylactic cranial radiation not only reduced the incidence of brain metastases but also improved disease-free and overall survival rates. Thus, PCI should be offered to all responding patients with extensive stage small cell lung cancer and should be considered standard of therapy for this stage of the disease in these patients.
- Management of relapse: Patients with relapsed small cell lung cancer have an extremely poor prognosis. Those whose disease does not respond to or progresses on initial treatment (ie, those with refractory disease) or those whose disease relapses within 6 months of completion of therapy have little chance of responding to additional chemotherapy. In general, PE given after CAV failure produces better response rates than CAV given after PE. Topotecan received US Food and Drug Administration (FDA) approval for use in chemotherapy-sensitive disease after failure of front-line chemotherapy. Because of the lack of long-term benefit of this therapy, however, patients with relapsed or refractory small cell lung cancer should be encouraged to enroll in clinical trials, if their condition permits.
Surgical Care
See Medical Care.
Consultations
Patients in whom lung cancer is suspected may require consultation with a pulmonologist to establish a diagnosis. Once a diagnosis is established, medical and radiation oncologists should be consulted to complete the staging workup and devise a management plan.
Diet
Weight loss is an important factor indicating poor prognosis in patients with small cell lung cancer. A dietary consultation should be obtained for patients with persistent weight loss.
Activity
Performance status is another important prognostic factor. Patients who are ambulating less than 50% of waking hours have a worse prognosis. Activity should be encouraged.
Medication
The goals of pharmacotherapy are to induce remission, reduce morbidity, and prevent complications.
Antiemetic agents
Vomiting induced by antineoplastic agents is stimulated through the chemoreceptor trigger zone (CTZ), which then stimulates the vomiting center (VC) in the brain. Increased activity of central neurotransmitters, dopamine in CTZ or acetylcholine in VC, appears to be a major mediator in inducing vomiting. Following administration of antineoplastic agents, serotonin (5-HT) is released from enterochromaffin cells in the GI tract. With serotonin release and subsequent binding to 5-HT3 receptors, vagal neurons are stimulated and transmit signals to the VC, resulting in nausea and vomiting.
Antineoplastic agents may cause nausea and vomiting so intolerable that some patients refuse further treatment. Some antineoplastic agents are more emetogenic than others. Prophylaxis with antiemetic agents prior to and following cancer treatment is often essential to ensure administration of the entire chemotherapy regimen.
Metoclopramide (Clopra, Reglan, Maxolon, Octamide PFS)
Dopamine antagonist that stimulates acetylcholine release in myenteric plexus. Acts centrally on chemoreceptor triggers in floor of fourth ventricle, which provides important antiemetic activity.
Adult
5-10 mg PO or 5-20 mg IV/IM tid
Pediatric
Not established
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
Documented hypersensitivity; pheochromocytoma; GI hemorrhage, obstruction, or perforation; history of seizure disorders
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in breastfeeding women, depression, hypertension, Parkinson disease, and conditions aggravated by anticholinergic or antidopaminergic effects; may cause tardive dyskinesia
Dexamethasone (Decadron)
Synthetic adrenocortical steroid with multiple indications. Widely used in combination with serotonin receptor antagonists in prevention of nausea and vomiting caused by highly emetogenic agents (eg, cisplatin).
Adult
8-20 mg PO/IV 30 min prior to chemotherapy combined with 5-HT3-receptor antagonist
Pediatric
Not established
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
Documented hypersensitivity; active infection
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
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
Ondansetron (Zofran)
Selective 5-HT3-receptor antagonist. Unclear whether effect is centrally and/or peripherally mediated. Used to prevent chemotherapy-induced nausea and vomiting.
Adult
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
Pediatric
Not established
Although potential for cytochrome P-450 inducers (eg, barbiturates, rifampin, carbamazepine, phenytoin) to change half-life and clearance, dosage adjustment usually not required
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Administer for prevention of nausea and vomiting, not for rescue of nausea and vomiting; headache occurs commonly (up to 40%)
Granisetron (Kytril)
Selective 5-HT3-receptor antagonist. Unclear whether effect is centrally and/or peripherally mediated. Used to prevent chemotherapy-induced nausea and vomiting.
Adult
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
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
To be administered for prevention of nausea and vomiting, not for rescue of nausea and vomiting; caution in liver disease
Dolasetron (Anzemet)
Binds to 5-HT3 receptors located on vagal neurons in GI tract, blocking signal to VC, thus preventing nausea and vomiting.
Adult
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
Pediatric
Not established
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
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
To be administered for prevention of nausea and vomiting, not for rescue of nausea and vomiting; may prolong QT interval, mildly elevates LFTs
Palonosetron (Aloxi)
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.
Adult
0.25 mg IV once (30 min before chemotherapy); administer over 30 sec; do not repeat dose within 7 d
Pediatric
<18 years: Not established
None reported
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
May cause headache, constipation, diarrhea, or dizziness
Antineoplastic agents
Used in curative therapy of limited-stage small cell lung cancer or to prolong survival in extensive-stage disease. 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 (ie, cell-cycle phase G1), followed by DNA synthesis (ie, phase S). The next phase is a premitotic phase (ie, G2); then, finally, mitotic cell division (ie, phase M) occurs.
The cell division rate varies for different tumors. Most common cancers grow very slowly compared with the growth rate of normal tissues, and the rate may decrease further in large tumors. This difference allows normal cells to recover more quickly from chemotherapy than malignant ones, which is the rationale behind current cyclic dosage schedules. Dosage cycles are determined by cancer stage and tolerance of adverse effects.
Antineoplastic agents interfere with cell reproduction. Some agents are cell-cycle specific, while others (eg, alkylating agents, anthracycline, cisplatin) are not. Cellular apoptosis (ie, programmed cell death) also is a potential mechanism of action of many antineoplastic agents.
Etoposide (Toposar, VePesid)
Inhibits topoisomerase II and causes DNA strand breakage, causing cell proliferation to arrest in late S or early G2 portion of cell cycle.
Adult
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
Pediatric
Not established
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
Documented hypersensitivity; IT administration (may cause death)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
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
Cyclophosphamide (Cytoxan, Neosar)
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.
Adult
CAV or CAVE regimens: 1000 mg/m2 IV on day 1 of cycle, repeat every 3-4 wk for 4-6 cycles
Pediatric
Not established
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
Documented hypersensitivity; severely depressed bone marrow function
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis
Doxorubicin (Adriamycin, Rubex)
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.
Adult
CAV or CAVE regimens: 50 mg/m2 IV on day 1 of cycle, repeat every 3-4 wk for 4-6 cycles
Pediatric
Not established
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; completed cumulative doses of anthracyclines or anthracenes; preexisting myelosuppression
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 with impaired hepatic function
Vincristine (Oncovin)
Inhibits tubulin polymerization during mitosis. G2 phase specific.
Adult
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
Pediatric
Not established
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
Documented hypersensitivity; IT administration (may be fatal)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in severe cardiopulmonary impairment, hepatic impairment (decrease dose), or preexisting neuromuscular disease
Topotecan (Hycamtin)
Inhibits topoisomerase I, inhibiting DNA replication.
Adult
IV: Single-agent regimen: 1.5 mg/m2/d IV over 30 min days 1-5 of cycle, repeat every 3-4 wk for 4-6 cycles
PO: 2.3 mg/m2/d PO qd for days 1-5 of cycle; repeat q21d
Modify dose with bone marrow toxicity or grade III/IV diarrhea
Pediatric
Not established
Other antineoplastics may result in prolonged neutropenia and thrombocytopenia, in addition to increased morbidity/mortality
Documented hypersensitivity; bone marrow suppression; renal dysfunction
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Adverse effects include myelosuppression and neutropenic fever, dermatitis, nausea, and vomiting; monitor bone marrow function; decrease dose in renal failure
Paclitaxel (Taxol)
Mechanisms of action are tubulin polymerization and microtubule stabilization.
Adult
200 mg/m2 IV on day 1 of cycle, repeat every 3-4 wk for 4-6 cycles
Pediatric
Not established
Cisplatin may further increase myelosuppression; 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
Documented hypersensitivity; peripheral neuropathy; bone marrow suppression; liver failure; severe cardiac disease
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Premedicate with corticosteroids, H1 and H2 blockers to decrease risk of hypersensitivity reactions; myelosuppression, alopecia, arthralgia/myalgias, and cardiac arrhythmias may occur; is vesicant, use extravasation precautions; decrease dose in hepatic impairment
Carboplatin (Paraplatin)
Analog of cisplatin (ie, platinum-salt alkylating agent). Has similar efficacy as cisplatin but with lower toxicity profile. Mechanism of action for cisplatin and carboplatin is production of cross-links within and between strands of DNA.
Adult
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
Pediatric
Not established
Nephrotoxicity and ototoxicity increase with aminoglycosides and other nephrotoxic drugs
Documented hypersensitivity; bone marrow suppression
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
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
Cisplatin (Platinol)
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. Forms backbone of currently available approved combination chemotherapy regimens for NSCLC and SCLC.
Adult
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)
Pediatric
Not established
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
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 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
More on Lung Cancer, Oat Cell (Small Cell) |
| Overview: Lung Cancer, Oat Cell (Small Cell) |
| Differential Diagnoses & Workup: Lung Cancer, Oat Cell (Small Cell) |
 Treatment & Medication: Lung Cancer, Oat Cell (Small Cell) |
| Follow-up: Lung Cancer, Oat Cell (Small Cell) |
| References |
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References
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Further Reading
Keywords
small cell lung cancer, SCLC, non–small-cell lung cancers, NSCLCs, lung cancer treatment, lung cancer diagnosis, lung cancer symptoms, small cell carcinoma, SCC, oat cell carcinoma, paraneoplastic syndromes, tumor suppressor genes
