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.

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 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.

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

We treated 28 patients who had no prior chemotherapy for stage IV breast cancer and 51 patients with extensive prior exposure to other chemotherapeutic agents with a 24-hour infusion of Taxol (paclitaxel) as a single agent. Prophylactic recombinant human granulocyte colony-stimulating factor was administered routinely to ameliorate the anticipated dose-limiting toxicity of neutropenia. Nonhematologic toxicity was mild to moderate in most cases. Taxol was more active in patients with chemotherapy-naive stage IV disease, but activity was also observed in extensively treated patients as well. There is a strong clinical suggestion of at least partial noncross-resistance with doxorubicin. Taxol is a very promising agent for the treatment of metastatic breast cancer; its optimal application in this disease will be the subject of future trials.

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.

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.

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.

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.

Randomized prospective trial of 5 versus 10 cycles of cyclophosphamide, doxorubicin, and cisplatin in advanced ovarian carcinoma.

Five versus ten cycles of cyclophosphamide, doxorubicin, and cisplatin (CAP) were compared in advanced ovarian carcinoma by a prospective randomized study of 78 patients, 41 receiving 5 cycles (CAP5) and 37 receiving 10 cycles (CAP10) of chemotherapy. Patients were stratified by histologic grade and size of residual disease. Cyclophosphamide, 600 mg/m2, doxorubicin, 40 mg/m2, and cisplatin, 100 mg/m2, were administered every 4 weeks for 5 or 10 cycles. Second-look laparotomy was performed to evaluate response and plan further therapy. CAP5 patients found a second-look laparotomy to have partially responded to chemotherapy were treated with 5 additional cycles of CAP. CAP10 was more toxic than CAP5 with respect to myelosuppression, hospital admissions for nadir fever, median elevation of creatinine, and degree of peripheral neuropathy. Median follow-up is 64 months. CAP5 and CAP10 were equivalent in surgically documented complete responses (34 versus 35%) and survival (P = 0.41). Twelve partial responders to CAP5 received additional CAP chemotherapy; one complete response resulted. We conclude that CAP5 is preferable to CAP10 in treatment of advanced ovarian cancer as it is equally effective and less toxic.

Prognostic factors for recurrence following negative second-look laparotomy in ovarian cancer patients treated with platinum-based chemotherapy.

Prior studies of the risk of recurrence following negative second-look laparotomy have included patients treated with a variety of chemotherapeutic regimens, including nonplatinum regimens. We have examined the long-term outcome and risk factors for recurrence among a homogeneous group of platinum-treated patients. During the years 1978-1987, 91 patients at Memorial Sloan-Kettering Cancer Center had a negative second-look laparotomy following platinum-based chemotherapy for epithelial ovarian cancer. The mean age at diagnosis was 57 years, with a range of 30 to 79. Distribution by stage was as follows: I, 10; II, 18; III, 57; IV, 6. The mean number of cycles of platinum prior to second-look surgery was 6.3. The mean number of biopsies taken at negative second-look laparotomy was 12. Lymph node biopsies were done in 47/91 (52%) of patients. Median follow-up from the date of second-look laparotomy was 54.6 months among survivors. Forty of ninety-one patients (44%) have had recurrence, almost 40% of which were outside the peritoneal cavity. The mean interval from negative second-look laparotomy to recurrence was 24 months (range, 2-70 months). By multivariate analysis the risk of recurrence was significantly related to stage (P = 0.017), histologic grade (P = 0.041), and the amount of tumor remaining after the first operation for ovarian cancer (P = 0.015). Recurrence by stage was as follows: stage I, 1/10 (10%); stage II, 5/18 (28%); stage III, 31/57 (54%); stage IV, 3/6 (50%). Recurrence by grade was as follows: grade 1, 4/18 (22%); grade 2, 11/28 (39%); grade 3, 25/45 (56%). There was no relationship between the risk of recurrence and the number of cycles of platinum, the number of biopsies performed at second-look, or the number of months from primary surgery to second-look. Patients having negative second-look laparotomy following platinum-based chemotherapy for advanced epithelial ovarian cancer have a substantial risk of recurrence, particularly within the first 3 years. Such patients should be offered participation in clinical trials of consolidation therapy directed against both intraperitoneal and extraperitoneal disease.

Cisplatin-based combination chemotherapy in carcinoma of the fallopian tube.

Forty-three cases of primary tubal adenocarcinoma were treated at Memorial Sloan-Kettering Cancer Center between 1979 and 1989. Thirty-eight patients who received cisplatin-based combination chemotherapy following primary surgery were reviewed. The mean patient age was 59 years, with 86% postmenopausal. Distribution by stage was as follows: I, 3 (7%); II, 4 (11%); III, 27 (71%); and IV, 4 (11%). Median follow-up from the time of diagnosis was 62 months (range, 5-132). Overall survival for all 38 patients by Kaplan-Meier analysis was 51% at 5 years. Excluding stage I, patients with no residual disease following surgery had a significantly higher 5-year survival (83%) than those left with gross residual disease (28%). Twenty-six patients underwent a second-look procedure. Of the 21 patients with advanced (stages III, IV) disease undergoing reexploration, 11 (52%) had a negative second-look and 10 (48%) were positive. Ten of the eleven patients with a negative second-look remain clinically free of disease with a median follow-up of 49 months. One patient with stage III disease had recurred after 47 months. Carcinoma of the fallopian tube appears to respond favorably to cisplatin-based multiagent chemotherapy. Patients with advanced-stage disease who achieve a negative second-look appear to have an improved possibility of remaining disease-free over similar-stage patients with ovarian cancer.

Intraperitoneal chemotherapy: analysis of complications with an implanted subcutaneous port and catheter system.

To determine the morbidity associated with delivery of intraperitoneal chemotherapy via subcutaneous semipermanent infusion catheters, we analyzed the data on 227 patients treated from April 1985 through December 1989. A total of 249 catheters were inserted and used to administer chemotherapy in these patients. There were 40 (17.6%) complications associated with the use of 230 original catheters, with 20 patients experiencing catheter inflow obstruction and 20 developing catheter-related infections; the latter group included 8 patients with bowel perforations. Although there was a trend toward an increase in catheter-related infections in association with large bowel surgery and appendectomies, sample size limited statistical analysis. There were 7 (36.8%) complications associated with the use of 19 replacement catheters. This rate was significantly increased (P = 0.03) when compared with the complication rate of original catheters. This system functions well and has an acceptable level of morbidity for delivery of intraperitoneal chemotherapy in gynecologic cancer patients.

Interferon-alpha and gamma mediated gene responses in a human breast carcinoma cell line.

Interferons (IFNs) have been known to possess an antiproliferative effect on tumor cells besides their well characterized antiviral effect in cell cultures. The mechanism of action of the different IFNs is not fully understood, but in recent years a number of IFN-inducible genes, the presumed mediators of IFN action, have been identified. In the present study we examined the antiproliferative effect of IFN-alpha and IFN-gamma on human breast cancer cells (MCF-7) using (i) the MTT dye formation assay and (ii) anchorage-independent (AI) growth in soft agar. Both IFN-alpha and IFN-gamma were found to have an antiproliferative effect on the growth of MCF-7 cells. In addition, the kinetics of induction of a number of IFN-inducible genes was also examined. The expression of these genes was measured by mRNA analyses using specific [alpha-32P]-labeled cDNAs as probes. The induction of these genes by IFN-alpha and IFN-gamma is a primary effect of IFN, as de novo protein synthesis is not required for their induction. Our results on the kinetics of induction of these genes by IFN-alpha and IFN-gamma suggests a complex mechanism of ligand-dependent gene activation in this cell line with some similar and dissimilar pathways.

Chemotherapy-induced neutropenia and fever in patients receiving cisplatin-based chemotherapy for ovarian malignancy.

Fifty-six episodes of chemotherapy-induced neutropenia and fever occurred in forty-three patients receiving cisplatin-based combination chemotherapy for ovarian cancer. All patients were treated with broad-spectrum antibiotics including gentamicin. Twelve of fifty-six episodes were associated with positive cultures; in six patients a single organism was isolated, and the other six patients had polymicrobial infection. The mean duration of antibiotic therapy was 6.5 days. One patient died of sepsis. Fifty-five episodes had a successful outcome. There was no antibiotic-related morbidity. Based on this review we recommend broad-spectrum antibiotic therapy for chemotherapy-induced neutropenia with fever. The regimen of gentamicin plus ticarcillin and clavulanic acid (ceftazidime for penicillin-allergic patients) is effective as initial therapy. Additional agents (i.e., vancomycin) may be necessary in culture-positive patients based on sensitivity testing of bacterial isolates. Gentamicin can be safely administered to patients receiving cisplatin-based chemotherapy without compromising ability to continue cisplatin therapy in subsequent treatment cycles.

Association of disease-free survival and percent of ideal dose in adjuvant breast chemotherapy.

The relationship between percent of ideal dose and disease-free survival was examined in 256 Stage II and III patients who participated in a 2-year breast adjuvant chemotherapy trial consisting of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) given postoperatively. When analyzed analogously to previous work, the results confirmed a dose-response relationship: that is, there appeared to be an improved disease-free survival for patients receiving higher doses of adjuvant chemotherapy. The major criticism of such an analysis is its bias. This bias was addressed by considering only patients who were still receiving therapy at 6, 12, and 24 months; then, the dose-response relationship was no longer seen. Although causality cannot be inferred, the apparent differences in disease-free survival among the dose groups can be attributed to recurrences in the first 2 years among patients receiving lower doses of chemotherapy.

Aggressive chemosurgical debulking in patients with advanced ovarian cancer.

From July 1986 to June 1989, 43 evaluable patients with advanced ovarian cancer were treated on protocol with initial cytoreductive surgery, two courses of high-intensity intravenous Cytoxan (1000 mg/m2) and cisplatin (120-200 mg/m2) chemotherapy, and repeat debulking laparotomy in an effort to maximize response to a subsequent four cycles of intraperitoneal platinum-based chemotherapy. Two patients were stage IIIA, 2 stage IIIB, 28 stage IIIC, and 11 stage IV. Five tumors were grade 1, 9 grade 2, and 29 grade 3. Thirty-eight (88%) patients had bulky tumor (5-25 cm) found at first laparotomy; 25 of these had greater than 1-cm residual after initial debulking. Following two cycles of intensive intravenous chemotherapy 18 of these 25 had greater than 1-cm disease found at second laparotomy; 12 of 18 underwent secondary cytoreduction to less than 1 cm. Thus, 30 of these 38 (79%) patients entered the intraperitoneal phase of the protocol with less than 1-cm disease. Four patients had 2- to 5-cm tumor at initial laparotomy; two of four were debulked to less than 1-cm residual. All four were found to have less than 1-cm disease at second laparotomy. This combination regimen was well tolerated. There was one treatment-related death. In sum, 42 of 43 patients had tumor greater than 2 cm at staging laparotomy and 38 (88%) had large, bulky disease (5-25 cm); 34 of 43 (79%) entered the intraperitoneal phase of the protocol with optimal (less than 1-cm) disease. Aggressive chemosurgical cytoreduction in patients with bulky advanced ovarian cancer can leave a large proportion of patients with minimal residual disease and maximize their chances of responding to subsequent intraperitoneal chemotherapy.

Expression of P-glycoprotein in epithelial ovarian cancer: evaluation as a marker of multidrug resistance.

The multidrug-resistance gene, MDR1, encodes a plasma membrane glycoprotein termed P-glycoprotein that mediates active cellular efflux of certain chemotherapeutic agents. P-Glycoprotein expression was evaluated in 98 frozen tumor specimens from 57 patients with epithelial ovarian cancer by the indirect immunoperoxidase technique with monoclonal antibodies C219 and JSB-1 used for detection. Tumor specimens were further characterized antigenically with a panel of monoclonal antibodies representing a variety of epithelial cell antigens. Included were 57 specimens from 33 previously untreated patients; 11 specimens were also available from eight patients in this group after chemotherapy. An additional 30 specimens were studied from 24 other patients after chemotherapy. In only four of the 57 patients with ovarian cancer (7%) did one or more of the specimens express P-glycoprotein. Two of these patients had tumors that were considered clinically drug resistant. No increase in P-glycoprotein expression was noted after exposure to chemotherapy, including the eight individuals for whom specimens were available both before and after treatment. Although drug resistance is a major problem in treatment of ovarian cancer, resistance to the drugs most active against these tumors probably occurs through a mechanism other than expression of the MDR1 gene product.

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.