Prognostic factors in advanced ovarian carcinoma.

Nineteen factors were analyzed for prognostic significance in a series of 89 women with advanced (stage III or IV) ovarian carcinoma treated with chemotherapy after initial debulking surgery. Seventy-eight of these women received cyclophosphamide, Adriamycin (Adria Laboratories, Columbus, Ohio), and cisplatin (CAP) treatment, and 11 received cyclophosphamide initially with Adriamycin and cisplatin administered at the time of recurrence. Median survival and remission duration were 25 and 19 months, respectively. Using survival as an end point, significant prognostic factors in univariate analyses included the total residual mass after debulking (P = .0007), largest residual mass after debulking (P = .0008), and stage (P = .0098). Using remission duration as an end point, significant prognostic factors in univariate analyses included total residual mass after debulking (P = .007) and the largest residual mass after debulking (P = .0020). The prognostic variables were then considered as possible predictors of survival in a multivariate analysis using the Cox proportional hazards model resulting in the following expression: lambda i(t)/lambda o(t) = exp(0.5928 (log TRM - 1.8117) + 0.6450 (stage - 0.3827) + 0.6673 (C4 - 0.4198) - 0.8596 (CAP - 0.8642)), where lambda i(t)/lambda o(t) is the risk of dying for a particular patient compared with the average risk of the entire group; log TRM is the log of the volume of the total residual mass in cm3 plus 1.0; stage = 0 if stage III, 1 if stage IV; C4 = 0 if cytologic grade is 1, 2, or 3 and 1 if grade 4; CAP = 0 if treatment is cyclophosphamide and 1 if CAP. Median survival times of patients with relative risk greater than 1 and less than 1 are 43 and 19 months respectively. If this model is confirmed in a prospective study, then it could be used to assign risk and assess treatment options for similar patients at diagnosis.

A pilot study of adjuvant therapy in patients with cervical cancer at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy.

The prognosis after surgical therapy (radical hysterectomy and pelvic lymphadenectomy) of stages IB and IIA carcinoma of the cervix is affected by several histopathologic findings within the resected specimen. Patients at high risk of recurrence include those with involved pelvic lymph nodes, lymphatic or vascular invasion in the cervix, tumor size greater than 4 cm, grade 3 lesions, adenosquamous histology, parametrial invasion, and evidence of locally metastatic (noncontiguous) disease. We report the results of adjuvant chemotherapy (cisplatin and bleomycin) and pelvic radiotherapy in 32 patients with cervix cancer deemed to be at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy. The continuous disease-free survival rate for the 32 evaluable patients in 84% at a mean and median follow-up time of 28 months. Three patients are dead of disease and two patients are alive after treatment of local recurrences giving a survival rate of 91%. The two patients who are alive after disease recurrence demonstrated only locally recurrent disease while the three patients who have died with recurrent disease relapsed both locally and systemically. Complications of this treatment program were not significantly greater than those observed in prior studies using the combination of surgery and adjuvant radiotherapy without chemotherapy. When compared with the results from historical controls in a large series of similar patients at the same institution, the results in this pilot study are encouraging and would seem to justify a randomized prospective clinical trial.

Paclitaxel as second and subsequent therapy for metastatic breast cancer: activity independent of prior anthracycline response.

PURPOSE: Two phase II clinical trials were performed to determine efficacy and tolerability of paclitaxel (Taxol; Bristol-Myers Squibb Co, Wallingford, CT) and granulocyte colony-stimulating factor ([G-CSF] Neupogen; Amgen, Inc, Thousand Oaks, CA) as second or subsequent therapy for metastatic breast cancer. PATIENTS AND METHODS: Paclitaxel plus G-CSF was administered as a second stage IV regimen to 25 patients with metastatic breast cancer at a dose of 250 mg/m2 intravenously over 24 hours. Fifty-two patients received paclitoxel plus G-CSF at 200 mg/m2 as a third or subsequent regimen (no restriction on number of prior regimens or on prior high-dose chemotherapy). All patients had received prior anthracycline treatment, and ultimately had progressive bidimensionally measurable disease. RESULTS: Twenty-five of 76 patients (32.8%) had a major objective response (95% confidence interval [CI], 14% to 37%). The median duration of response was 7 months (range, 1 to 20+). Responses were as likely in patients with disease demonstrated to be unresponsive to anthracycline, ie, de novo resistance (11 of 37, or 30%) as in those with disease that once exhibited anthracycline sensitivity, ie, acquired resistance, (10 of 31, or 32%). G-CSF administration was associated with febrile neutropenic episodes in 36 of 402 cycles (9%) in 16 of 76 patients (21%). CONCLUSION: Paclitaxel's clinically significant activity against metastatic breast cancer extends to patients with many prior chemotherapy regimens. The lack of impact of prior doxorubicin therapy on the likelihood of subsequent response to paclitaxel suggests an important role for this agent in the treatment of refractory metastatic breast cancer.

A prospective randomized comparison of epirubicin and doxorubicin in patients with advanced breast cancer.

Fifty-four patients with advanced breast cancer who had failed prior non-anthracycline combination chemotherapy were randomized to treatment with either epirubicin 85 mg/m2 or doxorubicin 60 mg/m2 intravenously every three weeks. Of 52 evaluable patients, 25% (six of 24) treated with epirubicin, and 25% (seven of 28) treated with doxorubicin experienced major therapeutic responses. The median duration of response to epirubicin was 11.9 months compared to 7.1 months with doxorubicin. Cardiotoxicity was monitored by serial multigated radionuclide cineangiocardiography performed at rest and after exercise. Laboratory evidence of cardiotoxicity was defined as a decrease in resting left ventricular ejection fraction of greater than 10% from the baseline value, or a decrease of 5% or greater with exercise compared with the resting study performed on the same day. Fifteen patients treated with epirubicin and 18 patients treated with doxorubicin had at least two determinations of left ventricular ejection fraction and were evaluable for laboratory cardiotoxicity. Using methods of survival analysis, the median doses to the development of laboratory cardiotoxicity were estimated to be 935 mg/m2 of epirubicin and 468 mg/m2 of doxorubicin. Four patients treated with epirubicin and five treated with doxorubicin developed symptomatic congestive heart failure. The median cumulative dose at which congestive heart failure occurred was 1,134 mg/m2 of epirubicin compared with 492 mg/m2 of doxorubicin. Fewer episodes of nausea and vomiting were observed in patients receiving epirubicin. Epirubicin is a new anthracycline with reduced cardiac toxicity, but preserved efficacy in the treatment of patients with advanced breast cancer.

Paclitaxel and recombinant human granulocyte colony-stimulating factor as initial chemotherapy for metastatic breast cancer.

PURPOSE: A phase II study of Taxol (paclitaxel; Bristol-Myers Squibb Co, Princeton, NJ) as initial chemotherapy for metastatic breast cancer was conducted. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was used to ameliorate myelosuppression, the anticipated dose-limiting toxicity. PATIENTS AND METHODS: Twenty-eight patients with bidimensionally measurable breast cancer who had not received prior chemotherapy for metastatic disease were treated. Taxol was administered at 250 mg/m2 as a continuous 24-hour intravenous (i.v.) infusion every 21 days. rhG-CSF was administered at 5 micrograms/kg/d subcutaneously on days 3 through 10. RESULTS: Objective responses were observed in 16 of 26 assessable patients (62%; 95% confidence interval, 41% to 80%). There were three (12%) complete responses (CRs) and 13 (50%) partial responses (PRs). Ten of 16 patients (63%) who had received prior adjuvant chemotherapy responded, which included one CR and four PRs among eight patients who had received prior doxorubicin-containing therapy. Responses were observed in all sites of metastatic disease. The median time to first objective response was 5 weeks (range, 1 to 14). Administration of rhG-CSF was associated with a short duration of neutropenia (median, 2 days with absolute neutrophil count < 500 cells/microL). Eight of 26 patients (31%) who received more than one course received subsequent therapy without dose reduction. One hundred seventy-eight cycles of treatment were administered, with a median of six cycles per patient (range, one to 19). Eight courses (4.5%) were associated with admissions for neutropenic fever. Twenty-two patients (79%) did not require admission for neutropenic fever. Treatment was well tolerated. Adverse effects included generalized alopecia in all patients. Myalgias, arthralgias, and peripheral neuropathy were mild. No hypersensitivity reactions and no cardiac toxicity were observed. CONCLUSION: Taxol is highly active as initial chemotherapy for metastatic breast cancer. Administration of rhG-CSF reduced the incidence, depth, and duration of neutropenia, compared with published prior experience. Further studies of Taxol in breast cancer, including combinations with other active agents, are clearly warranted.

Phase II and pharmacologic study of docetaxel as initial chemotherapy for metastatic breast cancer.

PURPOSE: Because docetaxel (Taxotere, RP 56976; Rhone-Poulenc Rorer, Antony, France) appeared to be active against breast cancer in phase I trials, we performed this phase II study. PATIENTS AND METHODS: Thirty-seven patients with measurable disease were enrolled. Only prior hormone therapy was allowed, as was adjuvant chemotherapy completed > or = 12 months earlier. Docetaxel 100 mg/m2 was administered over 1 hour every 21 days. Diphenhydramine hydrochloride and/or corticosteroid premedication was added after hypersensitivity-like reactions (HSRs) were seen in two of the first six patients. Pharmacokinetic studies were performed during cycle 1 for correlation with toxicity. RESULTS: Thirty-seven patients were assessable. Nineteen (51%) required dose reductions, usually for neutropenic fever. The median nadir WBC count was 1.4 x 10(3)/microL. HSRs were noted in 20 patients (54%). At a median cumulative dose of 297 mg/m2 (range, 99.6 to 424.5 mg/m2), 30 patients (81%) developed fluid retention, for which 11 (30%) subsequently stopped treatment. The first-cycle plasma area under the concentration-time curve (AUC) did not correlate with toxicity, although an ineligible patient with hepatic metastases (pretreatment bilirubin level 1.8 mg/dL) had an elevated AUC and died of toxicity. Responses were seen at all sites. On an intent-to-treat basis, there were two (5%) complete responses (CRs) and 18 (49%) partial responses (PRs). The overall response proportion (CRs plus PRs) was 54% (95% confidence interval, 37% to 71%). The median time to response was 12 weeks (range, 3 to 15) and the median duration was 26 weeks (range, 10 to 58+). CONCLUSION: Docetaxel is active for metastatic breast cancer. Neutropenia and fluid retention are dose-limiting. The AUC did not predict toxicity, but caution is warranted when treating patients with liver dysfunction. An understanding of the pathophysiology of the fluid retention may facilitate prevention. Frequent HSR may warrant prophylactic premedication.

Taxol plus recombinant human granulocyte-colony stimulating factor as initial and as salvage chemotherapy for metastatic breast cancer: a preliminary report.

Twenty-eight patients received Taxol as their first chemotherapy for stage IV breast cancer. An additional 51 patients with extensive prior exposure to other chemotherapeutic agents received Taxol as salvage therapy. We found significant activity for the drug in both situations, as well as a strong clinical suggestion of non-cross-resistance with doxorubicin. An excellent response in previously irradiated skin was noted in one case. The routine use of recombinant human granulocyte-colony stimulating factor seemed to ameliorate some of the dose-limiting toxicity of neutropenia. Other toxicity was mild to moderate in most cases. With further development, Taxol should play a significant role in the systemic management of breast cancer.

Preliminary experience with paclitaxel (Taxol) plus recombinant human granulocyte colony-stimulating factor in the treatment of breast cancer.

Single-agent paclitaxel (TAXOL) was administered to 79 patients with stage IV breast cancer. Twenty-eight patients had no prior chemotherapy (for metastatic disease), and 51 patients had extensive exposure to other chemotherapeutic agents before beginning the 24-hour paclitaxel infusion. Routine use of recombinant human granulocyte colony-stimulating factor helped to ameliorate neutropenia, the dose-limiting toxicity, in some cases. Other toxicity was generally mild to moderate. Paclitaxel was more active in patients whose stage IV disease had not yet been exposed to chemotherapy, but activity was seen in the patients previously treated extensively as well. There is a strong clinical suggestion of non-cross-resistance with doxorubicin. In one case, an excellent response in previously irradiated skin was seen. Paclitaxel is a very promising agent for the treatment of metastatic breast cancer.

Monoclonal antibodies detect occult breast carcinoma metastases in the bone marrow of patients with early stage disease.

Thirty-five to 40% of patients with operable breast carcinoma develop metastases after primary therapy. There is a need for more specific prognostic parameters to identify patients who are most likely to benefit from adjuvant therapy. The success of such treatment stems from its ability to eradicate preclinical microscopic metastases. The bone marrow is an accessible and frequent site of breast carcinoma metastases. Following studies of Redding et al. (16), we used monoclonal antibodies that recognize membrane and cytoskeletal antigens expressed by epithelial cells (C26, T16, AE-1) in an immunohistochemical assay to find cancer cells in bone marrow aspirates. The assay can detect one cancer cell among 50,000-100,000 hematopoietic cells. None of the 44 control bone marrows (from normal individuals and patients with leukemias and lymphomas) contained antigen-positive (extrinsic) cells. We found extrinsic cells in the bone marrow of 35% (18 of 51) of patients with operable breast carcinoma; no extrinsic cells were identified by routine bone marrow cytology in these patients. Twenty-seven percent (six of 22) of patients with negative lymph nodes had antigen-positive cells, while 41% (12 of 29) of patients with lymph node metastases had such cells. Similarly, 23% (three of 13) of patients with TNM stage I disease, 38% (13 of 34) of patients with stage II disease, and 50% (two of four) of patients with stage III disease had extrinsic cells. In those cases where extrinsic cells were identified, stage II patients with negative lymph nodes and patients with stage I disease were found to have fewer such cells in their marrow than patients with lymph node metastases and patients with stage II disease. These trends did not reach the level of statistical significance in this small number of patients. The presence of extrinsic cells did not correlate with tumor size of lymphatic invasion around the tumor. We conclude that the epithelial cells detected in the bone marrow of the patients with breast carcinoma were carcinoma cells based on the following criteria: (a) they expressed both membrane and cytoplasmic epithelia-specific antigens, (b) they possessed the cytologic characteristics of malignant epithelial cells, and (c) these cells were not detected in the bone marrow from normal individuals or patients with nonepithelial neoplasms involving the bone marrow. We have shown that the technique described here can detect occult metastases in bone marrow and that the presence of extrinsic cells correlates with some established predictors of prognosis. Long-term clinical correlative follow-up studies are now underway.

Second-look laparotomy in endodermal sinus tumor: a report of two patients with normal levels of alpha-fetoprotein and residual tumor at reexploration.

The role of second-look laparotomy in the management of patients with endodermal sinus tumor of the ovary is controversial. We report two women who converted to a normal alpha-fetoprotein (AFP) level during treatment with combination chemotherapy, yet were found to have residual endodermal sinus tumor at second-look laparotomy. In view of the limited experience with this rare disease, we continue to recommend second-look laparotomy for patients who have completed chemotherapy for endodermal sinus tumor of the ovary, regardless of the serum AFP level.

Second-look laparotomy in stage I ovarian cancer following comprehensive surgical staging.

OBJECTIVE: To evaluate the role of second-look laparotomy in patients with comprehensively staged stage I epithelial ovarian cancer. METHODS: We reviewed the medical records and obtained long-term follow-up on 54 stage I patients who had second-look laparotomies following complete surgical staging and chemotherapy. RESULTS: The distribution by stage was as follows: stage IA 18 (33%), stage IB two (4%), and stage IC 34 (63%). Eighteen patients (33%) had endometrioid tumors, 12 (22%) clear cell, 13 (24%) mucinous, eight (15%) serous, and three (6%) undifferentiated. Forty-four patients (82%) had grade 2 or 3 tumors. Thirty-eight (70%) were treated with platinum-based regimens and 16 (30%) received non-platinum regimens. At second-look laparotomy, tumor was identified in three women (5.5%). Stage, cell type, and grade did not predict the second-look laparotomy result, although no patient with a grade 1 tumor had a positive second-look laparotomy. With a mean follow-up of 48 months from second-look laparotomy, 11 women (22%) have had recurrences following negative second looks. Tumor grade was a strong predictor of recurrence following negative second-look laparotomy (P < .0001), with the risk of recurrence being 0% for grades 1 and 2 and 52% for grade 3. Substage, cell type, and chemotherapy type and duration did not predict recurrence. CONCLUSIONS: The likelihood of a positive second-look laparotomy is about 5% in well-staged stage I ovarian cancer. Patients with stage I, grade 3 tumors have a risk of recurrence of approximately 50% following negative second-look laparotomy.

Platinum-based chemotherapy of high-risk stage I epithelial ovarian cancer following comprehensive surgical staging.

OBJECTIVE: To determine the long-term outcome in patients with high-risk stage I epithelial ovarian cancer treated with adjuvant platinum-based chemotherapy following comprehensive surgical staging. METHODS: We conducted a retrospective review of 62 patients with stage IA and IB (grades 2 or 3) and stage IC (all grades) epithelial ovarian cancer treated with platinum-based chemotherapy following comprehensive surgical staging. Clinicopathologic correlations were performed using disease-free survival as the end point. RESULTS: The mean patient age was 47 years. The distribution by stage was IA in 19 (31%), IB in four (6%), and IC in 39 (63%). Eighty percent of the patients had grade 2 or 3 tumors. The distribution by cell type was as follows: clear-cell 22 (35%), endometrioid 15 (24%), mucinous 11 (18%), serous eight (13%), and undifferentiated six (10%). The patients underwent an average of six cycles of platinum-based therapy. With a median follow-up of 40 months among survivors, 15 patients (24%) have relapsed, at a median interval of 22 months from diagnosis. Relapses occurred primarily in the peritoneal cavity and retroperitoneal lymph nodes. No patient has been rendered free of disease after relapse. Patients with grade 3 tumors had an increased risk of relapse as compared to those with grade 1 or 2 tumors (46 versus 8%; P = .002). Patients with clear-cell tumors had a higher risk of relapse than those with other cell types (41 versus 15%; P = .05). There was no statistically significant relationship between risk of recurrence and substage. None of 11 patients with stage IA, grade 2 disease had recurrence. Actuarial 5-year disease-free survival for the entire group of 62 patients was 73%. CONCLUSION: Platinum-based chemotherapy for high-risk stage I ovarian cancer does not appear to improve survival over that previously reported with non-platinum regimens.

Anticipatory immune suppression and nausea in women receiving cyclic chemotherapy for ovarian cancer.

Nausea and immune function were assessed in 20 cancer patients in the hospital prior to chemotherapy and compared with assessments conducted at home. Proliferative responses to T-cell mitogens were lower for cells isolated from hospital blood samples than for home samples obtained several days earlier. Patients also experienced increased nausea in the hospital. Hierarchical multiple regression analyses indicated that decreased immune function in the hospital was not related to increased anxiety. The observed anticipatory immune suppression is consistent with the hypothesis that chemotherapy patients may develop conditioned immune suppression as well as conditioned nausea after repeated pairings of hospital stimuli with the emetic and immunosuppressive effects of chemotherapy.

Phase II study of idarubicin in advanced cervical carcinoma.

Idarubicin, an anthracycline analogue, was studied in a Phase II trial of 18 patients with advanced cervical carcinoma. Fourteen patients had received no prior chemotherapy (11 had received radiotherapy and three were untreated). All patients received at least two courses of idarubicin at a dose of 12.5 mg/m2 i.v. every 3 weeks. No responses were noted. Fifteen patients had uninterrupted progression of disease and three were stable for 4, 5, and 6 months respectively. Myelosuppression was the most common side effect. Idarubicin displayed no antitumor effect in 18 minimally pretreated cervical carcinoma patients.

Cisplatin in the treatment of metastatic breast carcinoma: A prospective randomized trial of two dosage schedules.

Thirty-seven patients with metastatic breast carcinoma were treated in randomized study with cisplatin 60 mg/m2 or 120 mg/m2 I.V. q3 weeks. Most patients were heavily pretreated, having received an average of four prior cytotoxic agents. Partial responses were seen in 4/19 patients initially receiving cisplatin 120 mg/m2 and 0/18 receiving 60mg/m2. One of the five patients responded when crossed over from cisplatin 60mg/m2 to cisplatin 120 mg/m2. Average duration of response was 3 months and responses were seen in soft tissue and lung metastases. Toxicity in the form of nausea, vomiting, and inanition significantly limited the use of cisplatin in this patient population. We conclude that cisplatin is active in breast carcinoma and that a cisplatin at 120 mg/m2 may be more effective than at 60 mg/m2. However the study stopped short of statistical significance due to the toxicities of nausea, vomiting, and inanition.

Toxoplasmosis. Problems in diagnosis and treatment.

Forty-two cases of Toxoplasma gondii infection were analyzed, 25 in patients with neoplastic disease and 17 in apparently normal patients. Infection in normal hosts was usually manifested by adenopathy and ran a benign course. Infection in patients with neoplastic diseases was usually manifested by fever and/or neurologic symptoms. Patients with leukemias and lymphomas, particularly Hodgkin's Disease, were at highest risk for infection. Most, but not all, patients developed serologic titers indicative of infection. T. gondii infections were fatal in all eight cases with central nervous system involvement despite treatment in five cases. Leukopenia was a significant complication of treatment with sulfadiazine and pyrimethamine despite the use of folinic acid.

Phase I clinical trial of doxorubicin and iproplatin combination chemotherapy in patients with breast cancer.

Forty-eight patients with advanced breast cancer were treated in a disease-specific phase I trial of doxorubicin and iproplatin combination chemotherapy. The doses of doxorubicin ranged between 30 and 50 mg/m2, and the doses of iproplatin ranged between 150 and 250 mg/m2. Myelosuppression was observed at all levels, but was dose-limiting at the highest level. In addition, nausea, diarrhea and malaise were prominent toxicities. Neither cardiac nor renal toxicity was encountered. Nine of 26 (35%) of previously untreated patients, and 5 of 22 (23%) previously treated patients demonstrated partial or complete responses. Although this combination possesses therapeutic activity, given its toxicities, further evaluation of doxorubicin in combination with iproplatin is not recommended.

A phase II trial of extracorporeal plasma immunoadsorption of patient plasma with PROSORBA columns for treating metastatic breast cancer.

BACKGROUND: Circulating immune complexes (CIC) have been implicated as a cause of malignancy-associated immunosuppression and disease progression. Previous attempts to remove CIC by pheresis or immunoadsorption over a Staphylococcus aureus protein A column have resulted in a few clinical responses, however the relationship between removal of CIC and tumor response in these trials is not clear. Based on these data, a Phase II trial of immunoadsorption over a Staphylococcus aureus protein A column was initiated for patients with metastatic breast cancer. The authors sought to correlate clinical response with amount of CIC eluted from the columns after immunoadsorption. METHODS: The potential role of extracorporeal immunoadsorption was determined using protein A columns in treating patients with advanced breast cancer. An immunoadsorbent column composed of protein A was bound covalently to an inert silica matrix (PROSORBA [IMRE Corporation, Seattle, WA] column). Patients underwent a 3-hour on-line procedure phlebotomizing 2000 ml of whole blood. Patient plasma was passed over PROSORBA columns to remove immunoglobulin G (IgG) and IgG-related CIC. The treated plasma then was reunited with formed elements and reinfused into the patient. Patients were treated three times per week for a total of 4 weeks. Analyses of tumor-associated Le(x)-containing CIC adsorbed on PROSORBA columns were performed using an enzyme-linked immunosorbent assay technique with a monoclonal antibody specific for the Le(x) moiety. RESULTS: Sixteen patients were entered in this Phase II study, with a mean age of 57 years (range, 40-69 years). All patients received prior treatment for Stage IV breast cancer. The median number of PROSORBA treatments was 12 (range, 1-15 treatments). No toxicities or major objective responses were seen noted the 16 patients. One patient with severe chest wall pain had a symptomatic response. The remaining patients all had disease progression. Analyses of column eluates from 11 patients in this study revealed no detectable Le(x)-containing immune complexes when compared with control subjects. CONCLUSIONS: Immunoadsorption over a Staphylococcus aureus Protein A column had no meaningful antitumor activity in patients with advanced breast cancer. In this cohort of patients, an elevated level of Le(x) CIC was not confirmed in the eluates of the column compared with a control group of patients without cancer.

Germ cell malignancies of the ovary: treatment with vinblastine, actinomycin D, bleomycin and cisplatin containing chemotherapy combinations.

Seventeen patients with malignant ovarian germ cell tumors were treated with vinblastine, actinomycin D, bleomycin and cisplatin containing combinations. Many of these patients were heavily pretreated. Thirteen patients had objectively measurable disease and ten (77%) had an objective response (CR or PR). Four patients had nonmeasurable disease or were treated in an adjuvant setting and all remain without evidence of disease. Extensive disease and poor performance status were poor prognostic factors. Induction portions of these treatment programs which contained cisplatin appeared most effective. Maintenance portions without cisplatin appeared less effective.