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Biomedical subjects

S N Wolff

Publications and source records attributed to S N Wolff.

At least 55 records · Page 3Linked to original sources
PubMed1991

Effective treatment of small-noncleaved-cell lymphoma with high-intensity, brief-duration chemotherapy.

Small-noncleaved-cell (SNC) lymphoma is a high-grade, biologically aggressive neoplasm notable for poor response to therapy, high relapse rate, and less than a 20% long-term survival. We treated 20 patients with SNC lymphoma with a novel chemotherapeutic regimen using intensive doses of chemotherapy at frequent intervals in the inpatient setting. All patients were previously untreated. Sixteen patients (80%) had stage IV disease. Most patients (95%) had at least one other characteristic associated with poor prognosis (bulky [greater than 10 cm] disease, multiple extranodal sites, poor performance status), and 85% had two or more characteristics associated with poor prognosis. Seventeen patients (85%) achieved a complete response (CR) to therapy, including all three patients with human immunodeficiency virus (HIV)-associated disease. There have been three relapses, all occurring less than 18 months after treatment, and two of three relapses occurred in patients who were unable to complete therapy. At a median follow-up of 29 months, 13 patients (65%) remain disease-free; the calculated 5-year actuarial disease-free survival is 60%. Toxicity, chiefly myelosuppression, was severe but manageable. There were two treatment-related deaths, both in elderly patients with poor performance status and advanced-stage disease. These data suggest that such a dose-intensive approach improves the response and survival of patients with SNC lymphoma.

Adult↗
PubMed1990

High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy.

Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.

Acute Disease↗
PubMed1990

The treatment of progressive non-Hodgkin's lymphoma with intensive chemoradiotherapy and autologous marrow transplantation.

Intensive chemoradiotherapy, with or without additional local radiotherapy, and unpurged autologous marrow transplantation was given to 68 patients with progressive non-Hodgkin's lymphoma. Responses were attained in 44 patients (65%, 95% confidence intervals [CI], 52% to 76%), including 37 who achieved complete responses. Fifteen patients (22%, 95% C.I. 13% to 34%) remain free of disease (including 11 continuously) at a median of 5.3 (range 3.1 to 9.1) years later. Higher Karnofsky scores (P less than .01, Mann-Whitney U test) and the absence of a history of prior radiotherapy (P = .02, chi 2 test) were associated with achievement of complete plus partial responses. Higher Karnofsky scores (P less than .01, Mann-Whitney U test) and less resistant disease status at transplantation (P = .04, chi 2 test) were significant when calculations were limited to complete responses. Karnofsky scores were also associated with the probability of freedom from progression (P = .02, log-rank) for responding patients. Also, Karnofsky scores and the absence of prior radiotherapy (P less than .01 and P = .01, respectively, log-rank) were associated with improved survival. Progressive lymphoma was the chief cause of failure; progression usually occurred less than 6 months after transplantation, most often at the sites of active disease before the transplant. However, five patients (including four with high-grade non-Hodgkin's lymphoma) suffered hematogenous patterns of relapse; four of these five patients had no prior history of marrow involvement. Other causes of mortality included interstitial pneumonitis, sepsis, hemorrhage and renal failure. Intensive chemoradiotherapy and autologous marrow transplantation produces durable remissions in some patients with progressive non-Hodgkin's lymphoma. Since such therapy is more effective when given to patients with signs of less advanced disease, earlier treatment would be the simplest way to produce improved results. However, improved conditioning regimens will also be needed, and measures to reduce occult lymphoma stem cell contamination with the autograft may also be required to increase the likelihood of cure in some patients.

Adolescent↗
PubMed1990

Use of rifampin as an effective chemoprotectant and antidote against microcystin-LR toxicity.

Microcystin-LR (MCLR) is a potent cyclic heptapeptide hepatotoxin that is produced by the blue-green algae, Microcystis aeruginosa. This organism forms blooms in freshwater lakes and ponds. Following ingestion of contaminated waters, deaths of wildlife and domestic animals frequently occur. Due to the lack of available methods and drugs for treating cases of poisoning with this toxin, development of an effective antidote to this toxin is needed. We have examined the ability of the semisynthetic antibiotic rifampin to prevent the toxicity of a lethal dose of MCLR in mice. A dose of 25 mg/kg rifampin given intraperitoneally coadministered with a lethal dose of MCLR (100 micrograms/kg) or given 30 or 60 min prior to the MCLR prevented deaths in all animals. Seventy-five percent of the mice were protected from lethality when 25 mg/kg rifampin was given 15 min after the administration of MCLR. The coadministration of 17.5 mg/kg rifampin prevented lethality in 50% of the mice treated with MCLR, while 25% of the mice survived when rifampin was administered 15 min after the MCLR. At 10 mg/kg rifampin the time to death following administration of MCLR was extended, but the animals did not survive. The results indicate that rifampin is an effective chemoprotectant and antidote against the toxicity of MCLR in mice which can be successfully administered after exposure to MCLR.

Animals↗
PubMed1990

Etoposide kinetics in patients with obstructive jaundice.

The kinetics and urinary excretion of etoposide and etoposide glucuronide were determined in 11 patients with obstructive jaundice (bilirubin greater than 2.0 mg/dL) and in 23 patients with normal renal and hepatic function. Mean (+/- SE) measurements of clearance (24.5 +/- 2.06 v 26.5 +/- 2.05 mL/min/m2), half-life (5.7 +/- 0.5 v 6.4 +/- 0.5 hours), and volume of distribution (12.4 +/- 1.1 v 13.7 +/- 1.6 L/m2) were not significantly different in patients with jaundice when compared with controls. Similarly, etoposide kinetics in three patients determined during a period of hyperbilirubinemia were not different from measurements made in the same patients following resolution of their obstructive jaundice. In patients with jaundice, 46% of an administered etoposide dose was excreted in the urine as etoposide compared with 35% in controls (P = .15). Urinary excretion of etoposide glucuronide accounted for 29% of an administered etoposide dose in control patients and 15% in those with hepatic obstruction (P = .03). Biliary etoposide excretion measured in four patients with T-tubes was insignificant (less than 2.0% of an administered dose). The calculated renal clearance of etoposide was 11.5 mL/min/m2 in patients with jaundice and 10.4 mL/min/m2 in controls (P = .53). Respective metabolic clearance was 4.9 and 6.9 mL/min/m2 in these two study groups (P = .13). Although hepatic metabolism of etoposide may be slightly decreased in patients with obstructive jaundice, a modest increase in renal etoposide excretion appears to compensate for this change, so that total clearance is similar in the patients with jaundice when compared with controls. No etoposide dose reductions appear to be needed in treating patients with obstructive jaundice who have normal renal function.

Biliary Tract↗
PubMed1990

High-dose N,N',N"-triethylenethiophosphoramide (thiotepa) with autologous bone marrow transplantation: phase I studies.

N,N',N''-triethylenethiophosphoramide (thiotepa) is a polyfunctional alkylating agent similar in structure to nitrogen mustard. Thiotepa (synthesized by American Cyanamid Company, Wayne, NJ) underwent clinical trials in the 1960s that showed that it was active against a wide variety of tumors. At a standard dose level (10 to 30 mg/m2), the dose-limiting toxicity is myelosuppression; other toxicities are infrequent. Therefore, high-dose phase I evaluation was encouraged by these observations. Approximately 217 patients have been treated with single-agent high-dose thiotepa administered intravenously daily over 2 hours for 3 days followed by hematopoietic stem cell rescue to prevent prolonged myelotoxicity. The total doses administered ranged from 135 to 1,575 mg/m2. As anticipated, myelotoxicity was substantial, with 180 mg/m2 being the highest dose not requiring stem cell rescue to ensure hematopoietic recovery. Extramedullary toxicities consisted of stomatitis, dermatitis, hepatoxicity, and central nervous system (CNS) toxicity. CNS toxicity was dose-limiting; other toxicities were problematic, ie, dose-dependent but not truly dose-limiting. The maximal tolerated dose of thiotepa is 900 to 1,125 mg/m2, with the lower dose being the maximal dose for evaluation in combination chemotherapy. In high-dose phase I evaluation, the overall response rate was approximately 50% with responses seen in a wide variety of solid tumors, lymphomas, and pediatric tumors. High-dose thiotepa appears to be an alkylating agent with broad-spectrum antitumor efficacy, which should add to the cytoreductive regimens for both solid and hematopoietic tumors.

Bone Marrow Transplantation↗
PubMed1989

High-dose thiotepa with autologous bone marrow transplantation for metastatic malignant melanoma: results of phase I and II studies of the North American Bone Marrow Transplantation Group.

We evaluated thiotepa in escalating dose in a broad phase I and II study using cryopreserved autologous bone marrow transplantation to assure hematopoietic recovery. Thiotepa was administered intravenously (IV) over two hours daily for three consecutive days followed in three to four days by marrow transplantation. The daily dose ranged from 60 to 525 mg/m2 (total dose, 180 to 1,575 mg/m2). A total of 71 patients with malignant melanoma were treated. Forty-three patients (61%) had received prior cytotoxic therapy and 28 were untreated. Sixty-two patients (87%) had melanoma disseminated to at least one visceral site, nine patients had skin and/or lymphatic metastases only. As of January 1, 1988 one patient was too early to be evaluated, 15 patients were inevaluable for tumor response, four patients had a complete response (CR), and 25 patients had a partial response (PR) to treatment. The response rates (95% confidence interval) for the 55 evaluable patients and for all 71 treated patients were 53% (40% to 65%) and 41% (30% to 53%), respectively. The median duration of response was 3 months, with a range of 1 to 31 + months. Three patients were alive and well without evidence of tumor more than 1 year after treatment. Analysis of patient subsets indicated that neither total dose, previous cytotoxic therapy, or sites of metastases influenced response rate. In this study, high-dose thiotepa has demonstrated a high response rate in patients with metastatic malignant melanoma with both PRs and CRs noted. Although most of the responses were not durable, 10% of the responses lasted more than 1 year. Future studies will evaluate additional methods for increasing the response rate and improving the duration of response.

Adult↗
PubMed1989

Dose-intensive chemotherapy in refractory germ cell cancer--a phase I/II trial of high-dose carboplatin and etoposide with autologous bone marrow transplantation.

Between September 1986 and March 1988, 33 patients with refractory germ cell cancer were entered on a phase I/II trial of two courses of high-dose carboplatin plus etoposide with autologous bone marrow support. All patients had extensive prior treatment and had either cisplatin-refractory disease (67%) defined as progression within 4 weeks of the last cisplatin dose or failed at least two cisplatin-based regimens (35%) including a cisplatin-ifosfamide salvage regimen. Patients received a fixed total dose of etoposide of 1,200 mg/m2 with each cycle. The carboplatin dose ranged from 900 mg/m2 to 2,000 mg/m2. Twenty of the 33 patients received the second cycle of therapy. Despite extensive prior therapy with cisplatin, neurotoxicity, nephrotoxicity, or hearing impairment with high-dose carboplatin and etoposide was unusual. The most common nonhematologic toxicity was moderate enterocolitis. The hematologic toxicity of this regimen was substantial at each dose level. All 53 courses were accompanied by granulocytopenic fevers. Seven of the 33 patients (21%) died from treatment. All of these deaths occurred during the granulocyte nadir, and five were related to documented sepsis. Overall, 14 of 32 patients (44%) evaluable for response obtained an objective response, including eight complete remissions. Four patients remain in complete remission, with three patients being continuously free of disease in excess of 1 year. Eight responders (including four complete remissions) had progressed while receiving cisplatin. We conclude that carboplatin and etoposide can be administered in combination at high dosages and this regimen may have curative potential for patients with germ cell tumors resistant to conventional-dose cisplatin-based therapies.

Adolescent↗
PubMed1989

Allogeneic marrow transplantation for refractory Hodgkin's disease.

Eight patients with refractory Hodgkin's disease received intensive combination chemotherapy conditioning with cyclophosphamide, carmustine (BCNU), and etoposide (VP 16-213), and allogeneic marrow transplants. All patients achieved complete responses. Three patients relapsed; two died of Hodgkin's disease and one of chronic graft-v-host disease (GVHD) and infection. In all, four patients died due to transplant-related toxicity. One patient developed a fatal B-cell lymphoproliferative disorder soon after transplantation, and died without evidence of Hodgkin's disease. One patient is alive and free of progression 29 months after transplantation. These data indicate that allogeneic marrow transplantation may be considered as therapy for selected patients with advanced Hodgkin's disease and, despite substantial toxicity, will occasionally result in long-term responses. Better patient selection would likely improve results.

Adolescent↗
PubMed1989

High-dose cytarabine and daunorubicin as consolidation therapy for acute myeloid leukemia in first remission: long-term follow-up and results.

In an effort to increase the proportion of patients with acute myeloid leukemia (AML) remaining in continued complete remission (CCR), we administered intensive postremission consolidation therapy with high-dose cytarabine (Ara-C) and daunorubicin. Eighty-seven patients, with a median age of 38 years (range, 7 to 71), received consolidation therapy after first complete remission was obtained with standard induction chemotherapy that included conventional doses of Ara-C. Consolidation therapy consisted of from one to three cycles of high-dose Ara-C (3 g/m2 intravenously [IV] over 1 hour every 12 hours for 12 doses) followed by daunorubicin (30 mg/m2/d IV bolus for 3 days). After completion of the high-dose Ara-C and daunorubicin, no further therapy was administered. Myelosuppression encountered with consolidation resulted in a median duration of neutropenia and thrombocytopenia of 3 weeks. Four patients (5%) died during consolidation due to infection and/or hemorrhage; 59% of patients experienced severe but nonfatal infectious or extramedullary organ toxicity. With a median follow-up of more than 3.5 years from diagnosis, the proportion of patients, by Kaplan-Meier product-limit estimate, remaining in CCR is 49% (95% confidence limits, 37% to 61%). In a Cox multivariate analysis, only age significantly (P less than .001) influenced the probability of remaining in CCR. The probability of remaining in CCR was 83%, 50%, and 23% for age groups of 25 or less, 26 to 45, and more than 45 years, respectively. These survival curves all have stable long-term plateaus, suggesting cure. In this study, the administration of brief, intensive nonmarrow ablative chemotherapy resulted in a large proportion of patients with AML remaining in CCR, results similar to those reported with allogeneic bone marrow transplantation. Relapse of acute leukemia was still the major reason for therapy failure, suggesting that more effective or additional postremission therapy will be required to further improve the likelihood of cure especially for older patients.

Adolescent↗
PubMed1989

Treatment of progressive Hodgkin's disease with intensive chemoradiotherapy and autologous bone marrow transplantation.

Twenty-six patients with progressive Hodgkin's disease after conventional chemotherapy received intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT); 19 also received additional involved-field radiotherapy. Twenty-one patients [81%, 95% confidence intervals (CI) 61% to 94%] attained complete (n = 18) or partial responses. Ten patients (38%, 95% CI 20% to 59%) are disease-free a median of 4.5 years later (range 3.5 to 7.0 years), including seven patients with continuous complete responses. The likelihood of overall response was not significantly influenced by any clinical or treatment variable examined. However, there was a trend favoring patients with higher Karnofsky scores, and higher scores were associated with attainment of complete responses (P = .06 and P = .02, respectively, Mann-Whitney U test). Both higher Karnofsky scores and shorter durations of disease before transplantation were associated with improved survival in a stepwise Cox multivariate analysis. The chief cause of failure was progression at sites previously involved with Hodgkin's disease. No patient relapsed in the marrow, and two of three patients with a history of marrow involvement with Hodgkin's disease achieved durable complete responses after transplantation. These data suggest that inadequate pretransplant conditioning, and not the reinoculation of occult tumor cells in the autologous marrow, caused most relapses. Fatal treatment-related toxicity occurred in six patients. Three patients died of idiopathic interstitial pneumonitis; each had previously received local mediastinal irradiation before intensive chemoradiotherapy. Intensive chemoradiotherapy and ABMT produces durable responses in some patients with Hodgkin's disease incurable with conventional therapy. Use of such therapies at the first sign of failure with conventional chemotherapy and development of more effective conditioning regimens should further improve results.

Adolescent↗
PubMed1988

Advanced ovarian cancer: long-term results of treatment with intensive cisplatin-based chemotherapy of brief duration.

STUDY OBJECTIVE: To determine the efficacy of a 6-month course of combination chemotherapy with hexamethylmelamine, cyclophosphamide, doxorubicin, and cisplatin (H-CAP) in the treatment of advanced ovarian carcinoma. DESIGN: Prospective, non-randomized, single-institution trial with a 6-month course of chemotherapy, followed by second-look laparotomy for restaging. Minimum follow-up after completion of therapy is 83 months. PATIENTS: Fifty-five patients with advanced (stage III or IV), intermediate- or high-grade epithelial carcinoma of the ovary. Twenty patients had limited residual tumor (3 cm or less maximal tumor diameter) after initial cytoreductive surgery; 35 had extensive residual disease. INTERVENTIONS: All patients received chemotherapy with hexamethylmelamine (150 mg/m2 body surface area orally on days 1 to 14), cyclophosphamide (350 mg/m2 intravenously on days 1 and 8), doxorubicin (20 mg/m2 intravenously on days 1 and 8), and cisplatin (60 mg/m2 intravenously on day 1). Courses were repeated at 4-week intervals; 41 patients (75%) received six courses; 10 patients received five courses, 3 patients received four courses, and 1 patients received three courses. Forty-seven patients underwent second-look laparotomy after completion of therapy; 8 had their disease restaged clinically. RESULTS: Fifty-three of fifty-five patients (96%) had either partial or complete response to treatment. Nineteen of forty-seven patients who had a second-look laparotomy had a surgically documented complete response; 17 of these 19 patients began chemotherapy with limited residual tumor. Ten patients (18%) remain disease-free 83 to 108 months after therapy, whereas three additional patients died of other diseases without clinical evidence of recurrent ovarian cancer. Nine of twenty patients who began chemotherapy with limited residual tumor remain disease-free, as compared to only 1 of 35 patients with more extensive tumor (P less than 0.001). All long-term, disease-free survivors had surgically documented complete response at second-look laparotomy. CONCLUSIONS: Treatment with cisplatin-based combination chemotherapy after aggressive cytoreductive surgery should be considered standard treatment for advanced ovarian carcinoma. Our intensive, 6-month course of treatment produced results comparable to those previously reported with prolonged treatment.

Adult↗
PubMed1988

Use of the BCR probe to demonstrate extramedullary recurrence of CGL with a T cell lymphoid phenotype following bone marrow transplantation.

A case of Philadelphia chromosome (Ph1) positive chronic granulocytic leukemia (CGL) is described in which the patient underwent successful treatment with supralethal chemoradiotherapy and allogeneic bone marrow transplantation (BMT) after transformation to blast crisis. Supraclavicular adenopathy developed 5 months after BMT and biopsy revealed a hematopoietic lymphoid neoplasm with an early T cell phenotype. A concurrent bone marrow was microscopically and cytogenetically normal. A metaphase chromosome preparation could not be obtained from nodal tissue. Lymph node DNA, however, was easily extracted and a rearrangement of BCR identical to that in the bone marrow prior to BMT was demonstrated indicating recurrent CGL rather than a de novo lymphoproliferative process. Appropriate therapy for lymphoid blast crisis resulted in a marked regression of measurable disease. The BCR probe may prove to be a useful tool for the diagnosis of CGL when standard cytogenetic techniques cannot be applied.

Adult↗
PubMed1988

Recent progress in the treatment of seminoma.

Effective treatment for seminoma of the testicle has improved markedly since the initial reports utilizing orthovoltage radiotherapy. Contributing to this progress have been the use of chemotherapy in advanced disease and the development of a staging system to predict outcome for patients treated with radiation therapy alone. Those groups of patients manifesting poor survival with radiation have benefited from cisplatin-based chemotherapy. At the present time, 80-100% of patients with limited disease and 60-80% of patients with more advanced disease will become long-term survivors. Areas requiring further investigation include the significance of elevated HCG, extragonadal primaries, residual radiographic abnormalities following chemotherapy, and the treatment of relapse after chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

High-dose chemoradiotherapy with syngeneic bone marrow transplantation for multiple myeloma: a case report and literature review.

We had the opportunity to treat a patient with progressive heavily pretreated multiple myeloma with high-dose chemoradiotherapy with hematopoietic rescue by syngeneic bone marrow transplantation. The patient was a 53-year-old male who had previously received melphalan, prednisone, 1,3-bis (2-chloroethyl)-l-nitrosourea (BCNU), vincristine, and standard radiation therapy. At the time of bone marrow transplantation, he had increasing bone pain, increasing M-protein (IgG kappa), and a bone marrow diagnostic of myeloma. The transplant regimen consisted of cyclophosphamide, 60 mg/kg intravenously for 2 days, and total body irradiation--1,200 rads given as 200-rad fractions, twice daily for three days. The transplant course was complicated by confusion, herpes simplex mucositis, fever, and two episodes of idiopathic diffuse interstitial pneumonia. Over the next 2 years the patient did well and was in immunologic and bone marrow complete remission. Unfortunately, 3 years after treatment, the myeloma relapsed with detectable M-protein. Three and one-half years after transplant, clinical relapse occurred with bone pain and lytic lesions necessitating additional radiation and chemotherapy. Salvage therapy has produced clinical improvement and the patient is alive almost 4 years from transplant and almost 7 years from diagnosis. Although intense chemoradiotherapy did not cure this patient, substantial control of a refractory tumor was observed. This case, together with other cases of intense therapy for myeloma which are reviewed in this paper, support the concept of high-dose therapy and should foster further investigation of high-dose therapy.

Bone Marrow Transplantation↗
PubMed1987

In vitro pharmacodynamic evaluation of VP-16-213 and implications for chemotherapy.

VP-16-213 (Etoposide) is an active antineoplastic agent which has undergone extensive evaluation of clinical dose escalation. To corroborate a putative dose-response relationship, we studied, in a modified clonogenic assay, various doses and durations of exposure. VP-16-213 at doses of 0.01, 0.05, 0.10, 0.50, 1.0, 5.0, and 10.0 micrograms/ml, each with exposure durations of 1, 3, 18, and 30 h, was studied in vitro against two human tumor cell lines, MOLT and 9812. The doses and durations of exposure were chosen to approximate some of the pharmacokinetic values achievable in either standard-dose or high-dose clinical studies. The results, summarized as linear regression lines, demonstrate with statistical significance (p less than 0.03) that there is correlation between dose and cytotoxicity and between dose X duration of exposure (representing the area under the concentration-time curve) and cytotoxicity. Our in vitro data thus support the concept of intensive use of VP-16-213 to maximize antitumor activity. However, how best to accomplish the manipulation of dose and duration of exposure is not yet clear and will be the subject of future clinical investigations.

Carcinoma, Bronchogenic↗
PubMed1987

High-dose induction chemotherapy with cyclophosphamide, etoposide, and cisplatin for extensive-stage small-cell lung cancer.

To exploit possible dose-response and combination drug synergism, 20 previously untreated patients with extensive-stage small-cell lung cancer (SCLC) received one or two courses of high-dose induction chemotherapy consisting of cyclophosphamide (100 mg/kg), etoposide (1,200 mg/m2), and cisplatin (120 mg/m2) (HDCEP). HDCEP was followed by four cycles of standard-dose cyclophosphamide (1,000 mg/m2), doxorubicin (40 mg/m2), and vincristine (1.4 mg/m2) (CAV). Response was determined after HDCEP and following CAV. Reevaluation included repeat bronchoscopy and chest computerized tomography (CT), as well as repetition of all initially abnormal studies. All patients were evaluable for response and toxicity. Overall response to HDCEP was 90%, with a complete response (CR) rate of 65% (95% confidence limits, 44% to 86%) and a partial response (PR) rate of 25% (95% confidence limits, 6% to 44%). All patients either maintained or improved their initial response while receiving CAV. Median duration of response was 6 months (range, 2 to 12 months) and median survival was 9.5 + months (range, 2 to 21 + months). All 37 courses of HDCEP were associated with leukopenia (less than 1,000/microL), 92% with thrombocytopenia (less than 20,000/microL), and 84% with fever of greater than 38.5 degrees C. Additional toxicities included bacteremia (24%), nausea and emesis (59%), mucositis (57%), diarrhea (38%), and hemorrhagic cystitis (5%). There were two treatment-related deaths due to infection. A third patient died 4 months after completing HDCEP with pulmonary fibrosis. Although response duration and median survival were not improved, HDCEP produced a high CR rate in ambulatory patients with extensive-stage SCLC.

Aged↗