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Biomedical subjects

F A Greco

Publications and source records attributed to F A Greco.

At least 19 recordsLinked to original sources

Megestrol acetate in cancer anorexia and weight loss.

High-dose megestrol acetate has been associated with increased appetite and weight. To examine the effects of high-dose megestrol acetate in the treatment of anorexia and weight loss in patients with advanced hormone-insensitive malignant lesions, a randomized double-blind placebo-controlled trial was conducted. Patients receiving megestrol acetate for 1 month reported a significant improvement in appetite and adequacy of food intake compared with those receiving placebo. A three-item scale measuring appetite, adequacy of food intake, and concern about weight revealed a higher improvement with megestrol acetate than with placebo. Patients who worsened while receiving placebo had similar favorable changes after the cross over to megestrol acetate. These data indicate that megestrol acetate may improve appetite and food intake in patients with advanced cancer.

Adult

A phase II trial of cisplatin and prolonged administration of oral etoposide in extensive-stage small cell lung cancer.

Etoposide is a schedule-dependent agent with greater activity against small cell lung cancer (SCLC) when a given dose is administered over several days compared with a 1-day administration of the same dose. In an attempt to capitalize on the schedule dependency of etoposide, 22 previously untreated extensive-stage SCLC patients were given cisplatin (100 mg/m2 on day 1) plus 21 days of low-dose, oral etoposide (50 mg/m2/d). Chemotherapy was repeated every 28 days for four cycles. Complete blood counts were monitored weekly, and etoposide was discontinued if either the leukocyte or platelet count dropped below 2000/microliters or 75,000/microliters, respectively. All 22 patients were evaluable for response; 18 had either a complete (9%) or partial response (73%), an overall response rate of 82% (95% confidence interval, 62% to 93%). The median response duration was 7 months, and the median survival was 9.9 months (range, 1 to 17+ months). Sixteen (73%) patients received all planned cycles of etoposide. In Cycle 1 of chemotherapy, the median leukocyte nadir was 2700/microliters (range, 100 to 6300/microliters), and median platelet nadir was 180,000/microliters (range, 51,000 to 397,000/microliters). Life-threatening leukopenia (less than 1000/microliters) was rare (3 of 74 cycles). There were three treatment-related deaths, only one of which was associated with neutropenia. One patient had mild renal insufficiency that resolved after discontinuation of therapy. Alopecia was observed in all patients, but other nonhematologic toxicities were uncommon. A randomized study is necessary to determine if this schedule of cisplatin and etoposide administration is superior to more standard methods. However, these data do not indicate a major survival benefit will be derived from increasing the duration of etoposide administration when used in combination with cisplatin given every 28 days.

Administration, Oral

Prolonged administration of oral etoposide plus cisplatin in extensive stage small cell lung cancer.

Etoposide is a highly schedule-dependent agent. We previously reported that a 21-day schedule of oral etoposide had good activity in small cell lung cancer (SCLC). The current phase II study was designed to test the combination of 21-day oral etoposide with cisplatin in hopes of capitalizing on etoposide's schedule dependency. Sixteen extensive stage SCLC patients were treated with cisplatin 100 mg/m2 day 1 plus 21 days of low-dose oral etoposide 50 mg/m2/day. Chemotherapy was repeated every 28 days for 4 cycles. Blood counts were monitored weekly, and etoposide was discontinued if the leukocyte or platelet count dropped below 2.0 x 10(9)/l or 75 x 10(9)/l, respectively. Fifteen of 16 patients were evaluable for response; 13 achieved either a complete (13%) or partial response (73%), for an overall response rate of 86% (95% confidence interval, 62-93%). Median response duration was approximately 7 months; median survival was not reached. Thirteen patients (81%) received all the planned cycles of chemotherapy. In cycle 1 of chemotherapy, the median leukocyte nadir was 2.8 x 10(9)/l (range, 0.1-6.3 x 10(9)/l; median platelet nadir was 180 x 10(9)/l (range, 51-397 x 10(9)/l). Life-threatening leukopenia (less than 1.0 x 10(9)/l) was unusual (2 of 58 cycles). There was 1 treatment-related death. One patient developed mild renal insufficiency that resolved after therapy. Nonhematologic toxicities were uncommon, but alopecia occurred in all patients. These data do not suggest that a major survival benefit will be derived for patients with extensive stage SCLC by increasing the duration of etoposide administration when used in combination with cisplatin. A randomized study is needed to determine if this long-term schedule of etoposide plus cisplatin is superior to the standard schedule of etoposide plus cisplatin.

Antineoplastic Combined Chemotherapy Protocols

Carboplatin plus oral etoposide in the management of unresectable non-small cell lung cancer. Preliminary results of a Vanderbilt trial.

Forty-two patients with unresectable non-small cell lung cancer (NSCLC) were treated with carboplatin (300, 350 or 400 mg/m2) and 21 days of oral etoposide (50 mg/m2/day). Thirty-three patients were evaluable for response (too early to assess the remaining patients) and 9 patients (27%) achieved a partial remission. Median survival was 29 weeks (range, 4+ to 71+ weeks). The primary toxicity was myelosuppression. Leukocyte and platelet count nadirs occurred between days 22 and 29. In cycle 1, median leukocyte nadir was 2.8 x 10(9)/l and the platelet nadir was 142 x 10(9)/l. Nonhematologic toxicities were modest and included alopecia in all patients, mild nausea, mild to moderate diarrhea, and an occasional increase in serum creatinine. Carboplatin plus oral etoposide is a tolerable outpatient regimen with modest activity against unresectable NSCLC.

Administration, Oral

Prolonged administration of oral etoposide in non-small-cell lung cancer: a phase II trial.

PURPOSE: The trial was undertaken to investigate the activity and toxicity of a prolonged schedule of oral etoposide in the treatment of advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Between March 1989 and August 1990, 25 patients with advanced NSCLC were treated with oral etoposide 50 mg/m2/d for 21 consecutive days, repeated every 28 to 35 days. The median patient age was 60 years (range, 38 to 84 years); male:female ratio was 12:13. Eight patients had stage IIIB disease; 17 had stage IV. Seventy-six percent of patients had Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. No patient had received previous chemotherapy with standard agents; nine patients had received previous or concurrent radiation therapy. Plasma etoposide concentrations were measured to estimate etoposide bioavailability and kinetics. RESULTS: Five of 22 patients (23%; 95% confidence interval [CI], 10% to 43%) had partial responses. Median response duration was 5 months (range, 2 to 6 months). Four of five responders were female. Besides alopecia, which occurred in all patients, myelosuppression was the most common toxicity, but was mild or moderate in most patients. Median leukocyte nadir during course 1 was 3,200/microL; only four of 69 courses produced a leukocyte nadir less than 1,000/microL. Severe thrombocythemia (less than 75,000/microL) did not occur. Gastrointestinal toxicity was uncommon. Median peak etoposide concentration was 3.4 micrograms/mL. A mean serum etoposide concentration greater than 1 microgram/L was maintained for more than 13 hours; the plasma concentration-time curve (AUC) was estimated to be 90% of that predicted after an identical dose of etoposide given intravenously. CONCLUSIONS: Etoposide given by this dose and schedule has moderate activity as first-line systemic therapy for advanced NSCLC. In previously untreated patients, chronic oral etoposide is well tolerated, and incorporation into combination regimens should be feasible. Etoposide bioavailability may be increased at lower oral doses.

Administration, Oral

Cisplatin-based combination chemotherapy in the treatment of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site: results of a 12-year experience.

PURPOSE: We previously reported excellent responses to cisplatin-based chemotherapy in a minority of patients with poorly differentiated carcinoma (PDC) or poorly differentiated adenocarcinoma (PDA) of unknown primary site. We have continued to study and to treat these patients, and now report clinical characteristics, treatment results, and prognostic factors in a large group of patients identified prospectively. PATIENTS AND METHODS: Between February 1978 and December 1989, we treated 220 patients with PDC or PDA of unknown primary site. The median age was 39 years; 48% of patients had predominant tumor location in the mediastinum, retroperitoneum, or peripheral lymph nodes. Specialized pathologic studies resulted in the identification of specific tumor types in only a few cases. All patients received cisplatin-based chemotherapy; between 1978 and 1984, 116 patients received cisplatin, vinblastine, and bleomycin (PVeB) +/- doxorubicin, and 104 patients treated since January 1985 received cisplatin and etoposide +/- bleomycin. RESULTS: One hundred thirty-eight patients (63%) had objective responses to therapy, and 58 (26%) had complete response. Thirty-six patients (16%) are currently disease-free at a median of 61 months following therapy (range, 11 to 142 months). Actuarial 10-year survival is 16%. Favorable prognostic factors identified by Cox regression analysis include: (1) predominant tumor location in the retroperitoneum or peripheral lymph nodes, (2) tumor limited to one or two metastatic sites, (3) no history of cigarette use, and (4) younger age. CONCLUSION: Patients with PDC or PDA of unknown primary site represent another group of patients for whom potentially curative therapy is available. Patients with this syndrome should be distinguished from patients with well-differentiated adenocarcinoma of unknown primary site, and should receive a trial of cisplatin-based chemotherapy.

Adenocarcinoma

Carboplatin plus oral etoposide in the management of advanced, non-small cell lung cancer: preliminary results of a Vanderbilt trial.

Twenty-eight patients with unresectable, metastatic non-small cell lung cancer (NSCLC) were treated with carboplatin/oral etoposide. Carboplatin was administered intravenously on day 1 at a dose of 300 mg/m2 (12 patients) or 350 mg/m2 (16 patients); oral etoposide was administered at a dose of 50 mg/m2/d for 21 consecutive days. Treatment was repeated every 28 days. Patient characteristics included male:female ratio of 23:5, median age of 60 years, median Eastern Cooperative Oncology Group performance status of 1, weight loss of 5% or more in seven patients; stage IIIB disease in two patients and stage IV in 26. Twenty-five patients were evaluable for response and seven (28%) achieved a partial response (95% confidence interval, 14% to 48%). Median duration of response was 3+ months (range, 2+ to 6+) and median survival was 4+ months (range, 1+ to 10+). Myelosuppression was the predominate toxicity; leukocyte and platelet nadirs occurred between days 22 and 29, with median counts of 2,900/microL and 172,000/microL, respectively. The median interval between the start of cycle 1 and the start of cycle 2 was 33 days (range, 26 to 42). Carboplatin/oral etoposide is a moderately active regimen against advanced NSCLC that can be administered in an outpatient setting with manageable toxicity. Its impact on survival remains to be determined.

Administration, Oral

Combination chemotherapy with oral etoposide.

Chronic administration of etoposide over multiple days has proved to be an effective schedule against a variety of neoplasms. The usual duration of etoposide administration is 3 to 5 days. However, recent studies have demonstrated this agent can be administered for up to 21 consecutive days with acceptable toxicity. Studies are currently under way to determine whether more protracted etoposide administration will prove to be more efficacious in the management of selected malignancies. Previous work at our institution has confirmed the activity of protracted administration of single-agent etoposide against small cell lung cancer and non-small cell lung cancer. More recently, we have combined either cisplatin or carboplatin with etoposide given orally for 21 consecutive days in phase II trials in patients with small cell lung cancer and non-small cell lung cancer. The results of these trials are reviewed.

Administration, Oral

Chronic oral etoposide in the treatment of lung cancer.

Etoposide is used commonly to treat both small cell lung cancer and non-small cell lung cancer. It is usually administered intravenously over 3 to 5 consecutive days, and usually given in combination with cisplatin. Preclinical cellular and clinical pharmacokinetic studies have demonstrated that etoposide is schedule-dependent and is optimally administered at low doses over prolonged periods of time. Recent early phase clinical trials have demonstrated that oral etoposide can be administered safely for 14 to 21 consecutive days. This schedule has demonstrated outstanding activity in patients with both recurrent and previously untreated small cell lung cancer. Activity against non-small cell lung cancer has also been reported; response rates are similar to those seen with the most active single agents used in the treatment of the disease. Chronic oral etoposide also has the advantages of outpatient convenience and tolerable side effects. This overview discusses the role of chronic oral etoposide in the management of small cell lung cancer and non-small cell lung cancer. The scientific rationale, results of early phase clinical trials, ongoing research, and future directions regarding the chronic administration of this important antineoplastic drug are also reviewed.

Administration, Oral

The role of cisplatin/bleomycin-based chemotherapy in the treatment of poorly differentiated carcinoma of unknown primary site.

Between 1978 and 1990, 173 patients with poorly differentiated carcinoma or poorly differentiated adenocarcinoma of unknown primary site were treated with bleomycin-containing regimens at Vanderbilt University Medical Center. Patients were prospectively identified based on light microscopy findings. The median age of patients was 39 years; 78% were male and 76% had metastatic tumors in two or more sites. Dominant tumor location was the mediastinum, retroperitoneum, or peripheral lymph nodes in 82 patients (47%). Between 1978 and 1985, patients received cisplatin 20 mg/m2 intravenously (IV) days 1 through 5, vinblastine 0.15 mg/kg IV days 1 and 2, and bleomycin 30 U IV weekly. In 1986, etoposide 100 mg/m2 IV days 1 through 5 replaced vinblastine in the regimen. Responding patients received four courses of therapy at 3-week intervals. One hundred thirteen patients (65%) had a major response to therapy, including 47 (27%) complete responses. At present, 27 patients are disease free at a median of 78 months posttherapy (range, 11 to 142 months); an additional patient was lost to follow-up while in complete response. Median survival of the entire group was 11 months, with a 12-year actuarial disease-free survival of 16%. Combination chemotherapy with cisplatin/bleomycin and either vinblastine or etoposide is highly active in patients with poorly differentiated carcinoma of unknown primary site and is curative in a minority of these patients. A trial of this therapy should be considered in all such patients.

Adenocarcinoma

Chronic etoposide schedules in the treatment of non-Hodgkin's lymphoma.

The importance of schedule in the cytotoxic efficacy of etoposide is supported by an increasing amount of clinical data. We studied the efficacy of oral etoposide (50 mg/m2/d x 21 repeated every 28 to 35 days) in the treatment of refractory lymphoma. Twenty-five patients were treated; all had received previous chemotherapy and were considered incurable. Fifteen patients (60%) had partial responses, including five of nine patients who had received previous intravenous etoposide. Median response duration was 8 months in patients with low-grade lymphoma and 3 months in those with intermediate- or high-grade lymphoma. Two patients responded to chronic oral etoposide immediately after disease progression with intravenous etoposide-containing regimens, demonstrating the improved efficacy of the chronic schedule. Single-agent oral etoposide, administered at 50 mg/m2/d for 21 days, provides an effective and convenient treatment option for patients with indolent lymphoma. Incorporation of this schedule into combination regimens for aggressive lymphoma is currently under investigation. In addition, we are exploring schedule modifications that may further decrease toxicity while maintaining efficacy.

Administration, Oral

Etoposide: seeking the best dose and schedule.

Etoposide is an important antineoplastic drug. Despite the use of several combination chemotherapy regimens that include etoposide, the best dose and schedule for etoposide remains unknown. The schedule dependency for small cell lung cancer is now known, and it is likely the same for other sensitive neoplasms (ie, lymphoma, germ cell tumors). Recent data suggest that even a more extended schedule of administration (ie, 14 to 21 days) may be more effective than the standard 3- to 5-day schedule. Several studies have assessed plasma levels in reference to dose, schedule, and tumor responsiveness. Preliminary data suggest that high peak levels (ie, > 5 to 10 micrograms/mL) are associated with more severe myelosuppression than lower peak plasma levels (ie, 1 to 3 micrograms/mL). Response rates and survival in small cell lung cancer patients given low daily doses for 14 to 21 days are comparable with results achieved with standard doses given for 3 to 5 days. Preliminary data from several studies suggest that administering low doses for a prolonged schedule is a superior method of etoposide administration. Other studies including randomized comparisons are necessary to confirm these observations.

Clinical Trials as Topic

Etoposide/cisplatin-based chemotherapy for patients with metastatic poorly differentiated carcinoma of unknown primary site.

Patients with poorly differentiated carcinoma (PDC) or poorly differentiated adenocarcinoma (PDA) of unknown primary site comprise a sizable minority (25% to 35%) of patients with carcinoma of unknown primary site. Some of these neoplasms are highly responsive to combination chemotherapy, and a minority of patients are curable. Between 1978 and 1982 we treated 67 patients with combination chemotherapy, most of whom received PVB (cisplatin/vinblastine/bleomycin) with or without doxorubicin. Thirty-eight patients (56%) responded to treatment, with 15 (22%) attaining complete responses (CRs). Nine patients (13%) are long-term disease-free survivors. Since that time, we have incorporated etoposide into our treatment program because of its synergism with cisplatin and its marked activity against several other neoplasms including germ cell tumors. Seventeen patients with PDC or PDA of unknown primary site received second-line therapy with etoposide/cisplatin after failing to respond to PVB. Ten of these patients had partial responses, with a median response duration of 5 months (range, 2 to 12). Eighty-five previously untreated patients with PDC or PDA received etoposide/cisplatin combinations as initial treatment; 57 of 78 evaluable patients (73%) responded to therapy, and 24 (31%) achieved CRs. Sixteen patients (19% of entire group) remain disease-free a median of 28 months (range, 9 to 66) after therapy. Etoposide is active against poorly differentiated carcinoma of unknown primary site. These results indicate that initial treatment with etoposide/cisplatin combinations is equivalent or superior to our previous results with PVB.

Adenocarcinoma

Neoadjuvant cisplatin plus vinblastine chemotherapy in locally advanced non-small cell lung cancer.

Twenty-eight patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) received neoadjuvant chemotherapy with cisplatin (120 mg/m2 on days 1 and 29) and vinblastine (4 mg/m2 weekly for 6 weeks). At the completion of induction chemotherapy, all patients were assessed for resectability. Those patients judged to be resectable underwent thoracotomy. All remaining patients received thoracic radiation therapy (5500 cGy) followed by additional chemotherapy in those patients responding to neoadjuvant treatment. There were 15 partial responses to neoadjuvant chemotherapy for an overall response rate of 54% (95% confidence interval, 36% to 71%). Only five partially responding patients (18%) were thought to have had sufficient tumor regression to allow for a potentially curative resection. However, a complete resection was done in only two patients. Overall median survival was 12 months (range, 4 to 72 months) with 1-year, 2-year, and 3-year survival rates of 54%, 39%, and 11%, respectively. The primary toxicity associated with neoadjuvant chemotherapy was moderate to severe (Eastern Cooperative Oncology Group Grade 3 or 4) nausea and emesis in 25% of patients. Hematologic toxicity was relatively modest; only one patient had Grade 4 leukopenia (less than 1000/microliter). Fever and neutropenia were uncommon, and there were no documented septic episodes or treatment-related deaths. Compared with historic controls treated with radiation therapy alone, cisplatin-based neoadjuvant chemotherapy appeared to improve the median and long-term survival of Stage III NSCLC patients modestly.

Adenocarcinoma

Results of treatment with high intensity, brief duration chemotherapy in poor prognosis non-Hodgkin's lymphoma.

A novel chemotherapeutic approach was designed for the treatment of intermediate and high-grade histology non-Hodgkin's lymphoma using augmented (but subtransplantation) doses of chemotherapy administered at frequent intervals in the inpatient setting. For the initial evaluation of this regimen, poor prognosis patients were treated with a projected long-term survival rate of less than 25% in response to standard therapy. Between March 1982 and May 1988, 56 previously untreated patients were entered into this study; all patients had either high-grade histology (20 patients) or predominantly large cell lymphoma (36 patients). Median age was 41.5 years (range, 18 to 69 years). Poor prognosis features included: Stage IV, 71%; poor performance status (Eastern Cooperative Oncology Group scale, 2 to 4), 55%; multiple extranodal sites of disease, 52%; elevated lactic dehydrogenase (greater than 300 IU/l), 43%; and bulky (greater than 10 cm) tumor masses, 30%. Thirty-three of 56 patients (59%) were in Shipp's Category 3. During the 6-year study, the chemotherapy regimen was modified in an attempt to improve efficacy and reduce toxicity. However, most patients received a 2-month course of therapy as follows: cyclophosphamide 1500 mg/m2 intravenously (IV) on days 1, 2, and 29; etoposide 400 mg/m2 IV on days 1, 2, and 3 and 100 mg/m2 on days 29, 30, 31; doxorubicin 45 mg/m2 IV on days 29, 30; vincristine 1.4 mg/m2 IV on days 8, 22, 36, and 50; bleomycin 10 units/m2 IV on days 8, 22, 36, and 50; methotrexate 200 mg/m2 IV on days 15 and 43 followed 24 hours later by leucovorin 15 mg/m2 IV every 6 hours for six doses; and prednisone 60 mg/m2 orally on days 1 to 7 and 29 to 35. The complete response (CR) rate was 77% (95% confidence interval, 64% to 86%). There were ten relapses, only one of which occurred after 18 months of follow-up. Overall event-free survival (EFS) was 52% (95% confidence interval, 36% to 68%), with a median follow-up of 36 months. Eleven of 13 patients with small noncleaved lymphoma had CR; actuarial EFS in this subgroup was 61%. Myelosuppression occurred in all patients, with severe leukopenia (less than 1000/microliters) lasting a median of 12 days (range, 3 to 29 days); toxic deaths occurred in five patients (9%; 95% confidence interval, 4% to 19%). This intensive approach improved the response and survival of very poor risk non-Hodgkin's lymphoma patients.

Adult

A brief-duration combination chemotherapy for elderly patients with poor-prognosis non-Hodgkin's lymphoma.

Curative combination chemotherapy is available for many patients with aggressive non-Hodgkin's lymphoma (NHL); however, treatment of elderly patients with these regimens is difficult due to excessive toxicity. From 1983 to 1988 the authors treated 26 patients 65 years and older with aggressive NHL with a novel 8-week chemotherapy regimen containing bleomycin, etoposide, cyclophosphamide, doxorubicin, methotrexate with leucovorin, and prednisone (BECALM), designed to preserve dose intensity and minimize toxicity. Median age was 75 years. Histologic types included the following: 20 intermediate grade (16 large noncleaved cell; two large cleaved cell; one intermediate grade, unspecified); six high grade (four small noncleaved cell; one immunoblastic sarcoma B-cell; one high grade, unspecified). Twenty-one patients were Stage III or IV. Twenty-two of 26 patients had one or more of the following: tumor greater than 10 cm; multiple extranodal sites; lactate dehydrogenase (LDH) 400 IU/l or greater; small noncleaved cell histologic type. Chemotherapy consisted of bleomycin 20 U intravenously (IV) weeks 1 and 7; etoposide 75 mg/m2 IV every day x 3 days on week 4; cyclophosphamide 600 mg/m2 IV weeks 1, 4, 7; doxorubicin 40 mg/m2 IV weeks 1, 7; methotrexate 50 mg/m2 IV weeks 1, 2, 4, 5, 7, 8 with oral leucovorin rescue; prednisone 60 mg orally for 10 days on weeks 1, 4, 7. Eighteen patients completed the 8-week treatment course. There were 13 complete responses (CR); seven patients remain in continuous CR at a median follow-up of 37.5 months. There have been five relapses, including one late relapse; and one patient died of an intercurrent illness in CR. Overall and actual event-free survivals are 38% and 27%, respectively. The major toxicities were neutropenic fever and mucositis. There were four treatment-related deaths. The authors conclude that BECALM chemotherapy can be administered to elderly patients with aggressive NHL. Although neurotoxicity and cumulative toxicity from bleomycin and anthracycline are avoided, the regimen remains moderately toxic, particularly with respect to myelosuppression. Treatment results compare favorably with other reported regimens in this group of patients with multiple poor prognostic features.

Aged

Current status of etoposide in the management of small cell lung cancer.

Etoposide is a schedule-dependent drug with excellent activity against small cell lung cancer (SCLC). Single-agent etoposide achieves overall response rates ranging from 15% to 84%, depending on the schedule of drug administration and the characteristics of the treated population. The route of etoposide administration (intravenous versus oral) has little impact on response rate, provided appropriate dose adjustments are made for oral therapy. In combination with other active agents, etoposide has proven particularly effective in the management of SCLC. Etoposide can be substituted for doxorubicin or vincristine in the cyclophosphamide, doxorubicin, and vincristine (CAV) regimen without loss of efficacy. The etoposide and cisplatin (EP) combination is thought to be synergistic and has proven to be an effective salvage regimen for CAV failures. A regimen that alternates CAV and EP has been found by some investigators to be modestly more effective against SCLC than CAV alone; however, EP alone may be as useful as an alternating regimen. Most studies to date have demonstrated that EP induction is at least as effective as any other standard induction regimen. However, EP has the potential advantage of being more easily integrated with thoracic radiation therapy (RT). This is particularly important in limited-disease patients: two recent pilot studies employing EP induction with hyperfractionated thoracic RT yielded 2-year survival rates of greater than 50%. These promising results are being evaluated further in an ongoing Phase III trial in the United States. The available data indicate that etoposide is one of the most active agents against SCLC and therefore should be included as a component of induction therapy in all patients. New schedules of etoposide administration warrant further study.

Antineoplastic Combined Chemotherapy Protocols