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Biomedical subjects

K R Hande

Publications and source records attributed to K R Hande.

At least 37 records · Page 2Linked to original sources
PubMed1996

Paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a phase II trial.

PURPOSE: Studies conducted by the Eastern Cooperative Oncology Group (ECOG) indicate both paclitaxel and carboplatin are associated with an improvement in 1-year survival in patients with stage IV non-small-cell lung cancer (NSCLC). Based on these findings, a phase II trial of these agents in combination was conducted in patients with advanced NSCLC. PATIENTS AND METHODS: Eligibility included previously untreated stage IIIB or IV NSCLC patients with a good performance status (PS). Paclitaxel (135 or 175 mg/m2) was administered by 24-hour infusion on day 1, followed by a 1-hour infusion of carboplatin on day 2 (300 mg/m2 or dosed to an area under the concentration-time curve [AUC] of 6 mg/mL.min). Treatment was repeated every 28 days for a total of six cycles. Hematopoietic growth factors were not routinely used. RESULTS: Among 51 eligible patients, there were no complete and 14 partial responses, for an overall response rate of 27% (95% confidence interval [CI], 17% to 41%). The median progression-free survival time was 23.8 weeks (range, 12.1 to 73.9) and median survival time, 38 weeks. The survival rate at 1 year was 32%. Grade 3 or 4 granulocytopenia and thrombocytopenia were observed in 47% and 3%, respectively, of the 184 treatment cycles administered. The most common nonhematologic toxicities included nausea and emesis, neuropathy, and arthralgia/myalgia. CONCLUSION: Paclitaxel plus carboplatin is a moderately active regimen in patients with advanced NSCLC and warrants comparison with existing cisplatin-based regimens in a prospective randomized trial. The toxicities of this regimen are well tolerated in patients with a good PS.

Adult↗
PubMed1996

Paclitaxel plus carboplatin in the treatment of patients with advanced lung cancer: a Vanderbilt University Cancer Center phase II trial (LUN-46).

In studies conducted by the Eastern Cooperative Oncology Group, treatment with either paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) or carboplatin was associated with an improvement in 1-year survival in patients with stage IV non-small cell lung cancer (NSCLC). Based on these findings, a phase II trial of carboplatin plus paclitaxel was conducted in patients with advanced NSCLC to determine the activity and toxicity of this regimen. Eligibility requirements included stage IIIB or IV histologically confirmed NSCLC, Eastern Cooperative Oncology Group performance status of 0 to 2, no prior chemotherapy, and adequate hematologic, renal, hepatic, and cardiac functions. Paclitaxel was administered intravenously over 24 hours at a dose of 135 mg/m2 (28 patients) or 175 mg/m2 (23 patients), followed by a 1-hour infusion of carboplatin on day 2. Carboplatin was administered at a dose of 300 mg/m2 (16 patients) or, using the Calvert formula, a dose calculated to achieve an area under the concentration-time curve of 6 mg/mL x min (35 patients). Treatment was repeated every 28 days for a total of six cycles. Among the 51 eligible patients, 34 were men and 17 were women; their median age was 60 years and their median Eastern Cooperative Oncology Group performance status was 1. Six patients had stage IIIB and 45 had stage IV disease. Grade 3 or 4 granulocytopenia and thrombocytopenia were observed in 47% and 3% of treatment cycles, respectively. The most common nonhematologic toxicities noted included nausea and emesis, neuropathy, and arthralgia and myalgia. There were no complete responses and 14 partial responses, for an overall response rate of 27% (95% confidence interval, 17% to 41%). Median survival was 38 weeks and the survival rate at 1 year was 32%. Paclitaxel plus carboplatin, as given in this study, was found to be a moderately active regimen in patients with advanced NSCLC. This regimen warrants comparison with existing cisplatin-based regimens in a prospective randomized trial.

Adult↗
PubMed1995

Cytochrome P-450IID6 phenotyping in cancer patients: debrisoquin and dextromethorphan as probes.

The usefulness of substituting dextromethorphan for debrisoquin as a probe for cytochrome P-450IID6 deficiency was investigated in 20 male cancer patients. Each patient was studied on two occasions. An oral dose of dextromethorphan (60 mg) was administered to 13 patients and are week later an oral dose of debrisoquin (10 mg) was administered to each patient. The order was reversed for the other 7 patients. An 8-h urine sample was collected after administration of each test drug and assayed for parent drug and metabolites. Five poor metabolizers (PMs) and 15 extensive metabolizers (EMs) of debrisoquin were tested. The debrisoquin metabolic ratio (DMR), calculated as [parent drug]/[metabolite], correlated with the metabolic ratio of dextromethorphan (R2 = 0.58, P = 0.0001). All PMs of debrisoquin (metabolic ratio > 12.0) were easily identified as being PMs of dextromethorphan (metabolic ratio > 0.30). Within the EM group, there was a significant correlation between the metabolic ratios of debrisoquin and dextromethorphan (R2 = 0.82, P < 0.0001). There was not as clear a correlation in the PM group (R2 = 0.32, P = 0.32). These findings suggest that dextromethorphan can be substituted for debrisoquin in establishing the debrisoquin phenotype in a patient population with metastatic cancer.

Aged↗
PubMed1995

Protection from cisplatin nephrotoxicity by A68828, an atrial natriuretic peptide.

The ability of a 13 amino-acid analog of atrial natriuretic peptide (ANP), A68828, to prevent development of cisplatin toxicity was evaluated in a rat model. ANP (1 microgram/kg/min), A68828 (10 micrograms/kg/min), A68828 (50 micrograms/kg/min), or peptide buffer was given as an intravenous infusion over 1 h beginning 15 min prior to an infusion of 5 mg/kg cisplatin. Animals receiving cisplatin plus peptide buffer vehicle developed predictable renal failure, with mean plasma creatinine and blood urea nitrogen concentrations of 1.09 +/- 0.09 mg/dL and 50.13 +/- 5.96 mg/dL, 72 h after treatment. ANP and A68828 (10 micrograms/kg/min) attenuated the increase in these indices of nephrotoxicity (mean plasma creatinine 0.86 +/- .06 mg/dL and 0.76 +/- 0.11 mg/dL, respectively). Surprisingly, the higher dose of A68828 (50 micrograms/kg/min) did not reduce cisplatin nephrotoxicity (72-h plasma creatinine 1.61 +/- 0.34 mg/dL). These results indicate that a short-term infusion of ANP or the analog A68828 can reduce the severity of cisplatin toxicity. At high doses of A68828 the beneficial effects of treatment may be lost.

Animals↗
PubMed1995

The role of the renin-angiotensin system in cisplatin nephrotoxicity.

The role of the renin-angiotensin system (RAS) in the pathogenesis of cisplatin nephrotoxicity was evaluated in an experimental rat model using a specific, nonpeptide angiotensin II(AII) receptor blocker, losartan. Rats were treated with a single dose of losartan (at 10 mg/kg and 30 mg/kg, i.p.) or saline, 2 h prior to cisplatin administration (5 mg/kg, i.p.). Renal function was assessed 3 and 7 days after cisplatin treatment. A second group of rats received losartan (10 mg/kg, i.p.) or saline, 2 h prior to cisplatin administration (5 mg/kg, i.p.), and losartan (10 mg/kg, i.p.) or saline daily for 6 days after cisplatin treatment. Renal function was assessed on day 7. Neither high- nor low-dose losartan pretreatment prevented development of cisplatin-induced nephrotoxicity. Blood urea nitrogen (BUN) and plasma creatinine values at 7 days were similar to those of animals receiving cisplatin alone (BUN: 17.12 +/- 1.1 and 22.17 +/- 2.2 vs. 20.58 +/- 2.4 mg/dL; creatinine: 1.04 +/- 0.05 and 0.82 +/- 0.09 vs. 0.84 +/- 0.06 mg/dL). A significant reduction in creatinine clearance with cisplatin treatment was seen 3 days after therapy, which was not prevented by pretreatment with losartan (GFR in controls: 2.1 +/- 0.16 mL/min; cisplatin: 0.24 +/- 0.05; cisplatin plus low-dose losartan: 0.05 +/- 0.03 and cisplatin plus high-dose losartan: 0.37 +/- 0.05). All groups of cisplatin-treated rats displayed systemic signs of cisplatin toxicity: reduced food intake and body weight. Rats receiving chronic losartan treatment had more rapid weight gain and lower BUN and plasma creatinine levels on day 7 than rats receiving cisplatin alone (BUN: 24.0 +/- 2.64 vs. 36.4 +/- 0.91 mg/dL; p < 0.05; plasma creatinine: 0.86 +/- 0.06 vs. 1.15 +/- 0.07 mg/dL; p < 0.05). Acute blockade of the AII receptor with losartan does not alter the onset or severity of cisplatin nephrotoxicity. Chronic blockade of the AII receptor may improve the rate of recovery of renal function in cisplatin-treated rats.

Angiotensin II↗
PubMed1995

Paclitaxel plus carboplatin for advanced lung cancer: preliminary results of a Vanderbilt University phase II trial--LUN-46.

Based on their good activity and minimal toxicity in non-small cell lung cancer and other cancers, we initiated a phase II trial of carboplatin plus paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of patients with previously untreated stage IIIB and IV non-small cell lung cancer. Among 51 patients treated, the overall response rate was 27.5% (14 partial responses). Seventeen patients had stable disease, while 16 patients experienced disease progression after two cycles of treatment. Apart from myelosuppression, toxicity has been modest, with fewer than 5% of patients experiencing grade 3 or greater nonhematologic toxicity. Objective response and survival rates were modestly improved among patients given the higher of two paclitaxel doses (175 mg/m2 v 135 mg/m2). These data suggest that paclitaxel plus carboplatin warrants further study in metastatic non-small cell lung cancer.

Adult↗
PubMed1994

Prolonged administration of low dose infusional etoposide in patients with advanced malignancies. A phase I/II study.

BACKGROUND: Etoposide displays remarkable schedule dependency. To better define the optimal dose and schedule, the authors administered etoposide as a prolonged low daily dose infusion in patients with a variety of advanced malignancies. METHODS: Between October 1989 and April 1992, 40 patients met inclusion criteria and were enrolled in this study; the initial dose of infusional etoposide was 25 mg/m2/day. Doses were not escalated further, because it became evident that 25 mg/m2/day was the maximum tolerated dose (MTD) in most patients using this prolonged schedule. Because the initial dose proved to be the MTD on this prolonged schedule, several patients received a starting dose of either 20 mg/m2/day or 18 mg/m2/day. This continuous infusion was administered for at least 21 days or until either the leukocyte count dropped to less than 2,000/mm3, platelets dropped to less than 75,000/mm3, or tumor progression occurred. Plasma etoposide levels were obtained at random times during infusions at 25 mg/m2/day. RESULTS: Duration of therapy ranged from 15-561 days. Myelosuppression was the major toxic reaction, although it was mild in most patients and reduced compared with other schedules. Myelosuppression correlated with the extent of prior treatment: minimally pretreated patients tolerated prolonged infusions with only mild hematologic toxic effects, whereas heavily pretreated patients experienced moderate myelosuppression. Patients treated at an initial dose of 25 mg/m2/day had more myelosuppression than did those treated at 20 mg/m2/day. A leukocyte count of less than 1,000/mm3 developed in only 5 of 40 patients (12%) at any time during therapy. Twenty-one patients required packed erythrocyte transfusions, and one required platelet transfusion. The mean serum etoposide concentration in patients receiving 25 mg/m2/day was 0.7 plus or minus 0.42 microgram/ml. Objective responses were obtained in 5 of 10 patients with previously treated non-Hodgkin's lymphoma and 2 of 3 patients with previously untreated extensive stage small cell lung cancer. CONCLUSIONS: Etoposide administered by continuous infusion can be given at 25 mg/m2/day for prolonged periods to most patients and is the MTD in previously treated patients. Tumoricidal activity in selected tumor types is demonstrated with this dose. Further study in neoplasms that considered "etoposide-sensitive" seems warranted.

Adult↗
PubMed1993

Acute tumor lysis syndrome in patients with high-grade non-Hodgkin's lymphoma.

PURPOSE: To identify patients with lymphoma at risk for tumor lysis after chemotherapy. PATIENTS AND METHODS: The case records of 102 patients receiving combination chemotherapy for non-Hodgkin's lymphoma (intermediate to high-grade histology) were reviewed. Patients were considered to have "laboratory tumor lysis" if two of the following metabolic changes occurred within 4 days of treatment: a 25% increase in the serum phosphate, potassium, uric acid, or urea nitrogen concentrations, or a 25% decline in the serum calcium concentration. "Clinical tumor lysis" was defined as laboratory tumor lysis plus one of the following: a serum potassium level greater than 6 mmol/L, a creatinine level greater than 221 mumol/L, or a calcium level less than 1.5 mmol/L, the development of a life-threatening arrhythmia, or sudden death. RESULTS: Laboratory tumor lysis occurred in 42% of patients and clinical tumor lysis in 6%. There was no statistical difference in the frequency of either tumor lysis syndrome among lymphoma subgroups. Clinical tumor lysis occurred more frequently in patients with pretreatment renal insufficiency (serum creatinine level greater than 132 mumol/L) than in patients with normal renal function (36% versus 2%; p = 0.01). The development of azotemia correlated with high pretreatment serum lactate dehydrogenase concentrations (p < 0.01; r2 = 0.11). CONCLUSION: Clinically significant tumor lysis is a rare occurrence in patients with lymphoma when they are receiving allopurinol. However, tumor lysis can occur in patients with all types of moderate to high-grade non-Hodgkin's lymphoma. Patients with a high serum lactate dehydrogenase level or renal insufficiency are at increased risk for metabolic complications after chemotherapy and should be closely monitored.

Acute Disease↗
PubMed1993

Bioavailability of low-dose oral etoposide.

PURPOSE: To determine the bioavailability of oral etoposide capsules administered at doses of 100 mg and 400 mg. PATIENTS AND METHODS: The bioavailability of oral etoposide was determined by measuring the area under the etoposide plasma concentration versus time curve (AUC) following intravenous (IV) etoposide administration and comparing that value to the AUC achieved following an oral dose administered 1 day later to the same patient. The bioavailability of a 100-mg oral dose of etoposide was measured on 16 occasions in 11 patients. The bioavailability of a 400-mg dose was determined on 12 occasions in six patients. RESULTS: The mean (+/- SD) bioavailability following a 100-mg dose of oral etoposide was 76% +/- 22%, which was significantly greater (P < .01) than the mean bioavailability of 48% +/- 18% following a 400-mg oral dose. The coefficient of variation in oral etoposide bioavailability was significant: 29% with a 100-mg oral dose and 37% with a 400-mg dose. CONCLUSION: Bioavailability of a 100-mg oral etoposide dose is greater than suggested in the package insert from Bristol Laboratories (Evansville, IN). Comparable oral etoposide doses are not uniformly twice that of an IV dose, as suggested by the package insert, but will depend on the final oral dose administered. Bioavailability is better at lower oral etoposide doses. This study confirms the wide interpatient and intrapatient variability in oral etoposide bioavailability.

Administration, Oral↗
PubMed1993

Prolonged administration of low-dose, infusional etoposide in patients with etoposide-sensitive neoplasms: a phase I/II study.

PURPOSE: This trial evaluated the activity and toxicity of a prolonged schedule of low-dose, daily infusional etoposide in patients with etoposide-sensitive neoplasms. PATIENTS AND METHODS: Fifteen patients (non-Hodgkin's lymphoma, n = 10; small-cell lung cancer, n = 3; germ cell neoplasm, n = 2) were treated. Ten had received etoposide previously. Etoposide 18 to 25 mg/m2/d was administered by continuous intravenous infusion for at least 21 days, or until either leukocyte count decreased to less than 2,000/microL, platelets decreased to less than 75,000/microL, or tumor progressed. Plasma etoposide levels were monitored during infusion. RESULTS: Duration of therapy ranged from 21 to 560 days; uninterrupted infusion ranged from 21 to 153 days. Seven patients (47%) had an objective tumor response (six partial, one complete), with a median duration of 7 months (range, 2 to 19). Myelosuppression limited the infusion; however, only four patients had grade 4 leukopenia, and most tolerated infusions with mild to moderate leukopenia. Nine patients required RBC transfusions. Only one patient developed severe thrombocytopenia. Alopecia was universal; however, other grade 3 or 4 nonhematologic toxicities were not encountered. The mean serum etoposide concentration was 0.7 +/- 0.42 microgram/mL. Only three patients had serum etoposide levels greater than 1 microgram/mL. CONCLUSION: Etoposide administered as a low-dose continuous infusion is active in etoposide-sensitive neoplasms. Myelosuppression is the major toxicity, but seems reduced when compared with other schedules. Tumor cytotoxicity was demonstrated with plasma levels ranging from 0.5 to 1.0 microgram/mL. Chronic low doses of etoposide may be superior to the standard dose and schedule and further study of this issue is warranted.

Adult↗
PubMed1992

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↗
PubMed1992

Antitumor antibiotics, epipodophyllotoxins, and vinca alkaloids.

This paper reviews manuscripts published from June 1991 to June 1992 that, in the author's opinion, have added to the understanding and clinical use of a group of commonly used antineoplastic agents. New developments highlighted include 1) clarification of the mechanism of action of the anthracyclines and epipodophyllotoxins, 2) evaluation of tests used for the early detection of bleomycin pulmonary toxicity, 3) results of studies on the epidemiology and prevention of anthracycline-induced cardiomyopathy, 4) the potential use of therapeutic drug monitoring to predict etoposide toxicity, and 5) identification of drug interactions that alter the pharmacokinetics of the epipodophyllotoxins.

Animals↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1992

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↗