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W J Hoskins

Publications and source records attributed to W J Hoskins.

At least 19 recordsLinked to original sources
PubMed2001

The role of laparoscopy in second-look evaluations for ovarian cancer.

BACKGROUND: The aim of this study was to evaluate the accuracy and safety of laparoscopic second-look operations in patients with ovarian cancer. METHODS: We retrospectively reviewed the medical records of all patients who have undergone laparoscopic second-look procedures for ovarian cancer at our institution. RESULTS: From July 1993 to December 1998, 150 patients underwent laparoscopic second-look operations. The mean age of patients was 53 years (range, 25-78 years). The majority of patients (87%) had Stage III or IV disease at initial surgery; the remainder were Stage II or unstaged. Eighty-two patients (54%) had had optimal cytoreduction at the time of their initial surgery. All patients had completed primary chemotherapy and were clinically disease-free based on imaging studies and CA-125 levels at the time of second look. Sixty-nine patients (46%) were found to have pathologically negative second looks; thus, the rate of positive second-look evaluations was 54%. The rate of conversion to laparotomy was 18/150 (12%). In 3 cases this was secondary to bowel injury; one patient sustained a bladder injury; the remainder of conversions to laparotomy were for secondary cytoreduction. There was only 1 case where the patient was found to have extensive adhesions and laparoscopy was abandoned. The overall rate of major complications was 2.7%. CONCLUSIONS: In our experience, laparoscopy is a safe and accurate method of second-look assessment in patients with ovarian cancer. The incidence of complications is low, particularly in this group of patients, all of whom have undergone prior abdominal surgery. The rate of negative evaluations and the rate of recurrences in patients with negative second looks are equivalent to those described in studies of second-look assessment by laparotomy.

Adult↗
PubMed2001

High incidence of positive peritoneal cytology in low-risk endometrial cancer treated by laparoscopically assisted vaginal hysterectomy.

OBJECTIVE: Laparoscopically assisted vaginal hysterectomy (LAVH) has evolved into an alternative form of surgical management in the treatment of low-risk endometrial cancer. The purpose of this study was to determine whether low-risk endometrial cancer patients are subject to a higher incidence of positive peritoneal cytology when treated with LAVH compared to total abdominal hysterectomy (TAH). METHODS: We retrospectively reviewed the medical records of patients with low-risk endometrial cancer (grade 1--2 endometrioid type with no evidence of extrauterine spread or grade 3 with <50% myometrial invasion (MI), no cervical or adnexal involvement, and negative lymph nodes when sampled) treated at Memorial Sloan-Kettering Cancer Center from January 1993 to September 1999. We compared 131 patients treated with LAVH to 246 controls who underwent TAH. The two groups were compared for known prognostic factors including grade, MI, vascular space involvement, and lower uterine segment extension. RESULTS: The mean age of patients who underwent LAVH (61 years) was similar to that of the controls (62 years). Fourteen (10.3%) of the patients treated with LAVH had positive peritoneal cytology compared to only 7 (2.8%) of the control population. Factors including FIGO grade, myometrial invasion, and preoperative hysteroscopy did not influence the final results. When stratifying for these factors, the odds ratios of having positive peritoneal washings in those patients treated by LAVH were 5.2, 5.2, and 3.7, respectively. CONCLUSION: Treatment of low-risk endometrial cancer by LAVH is associated with a significantly higher incidence of positive peritoneal cytology. This may be due to the retrograde dissemination of cancer cells into the peritoneal cavity during uterine manipulation. The clinical significance of these findings is yet to be determined.

Adult↗
PubMed2001

Identification of prognostic factors in advanced epithelial ovarian carcinoma.

OBJECTIVE: The Gynecologic Oncology Group (GOG) has demonstrated that age, tumor grade, and size and number of residual lesions after primary cytoreductive surgery are significant prognostic factors in advanced ovarian carcinoma. Recent studies have reported numerous other clinical features as having prognostic value. We sought to identify the independent prognostic factors for survival in a cohort of patients with advanced ovarian cancer. METHODS: We performed a retrospective chart review of all patients with stage III and IV ovarian carcinoma who received their primary treatment at our institution between 1987 and 1994. RESULTS: A total of 295 patients were identified, 282 of whom were evaluable. Of these 282 patients, 214 (76%) have died of disease or other causes. The median follow-up is 32 months (range: 1-139). Eighteen factors were evaluated for prognostic significance. Significant factors in univariate analysis included patient age, gravidity (0 vs > 0), parity (0 vs > 0), preoperative albumin level, preoperative total protein level, ascites (presence vs absence), disease stage (IIIA/IIIB vs IIIC vs IV), number of residual lesions (< or =20 vs >20), and diameter of largest residual tumor nodule (< or = 1 cm vs 1-2 cm vs > 2 cm). However, on multivariate analysis, only patient age (P < 0.001), ascites (P = 0.001), and size of residual disease (P = 0.005) retained prognostic significance. Substage of disease was of borderline significance (P = 0.086). CONCLUSION: Although numerous clinical variables have recently been reported to have prognostic value in advanced ovarian carcinoma, only patient age, presence or absence of ascites, and diameter of the largest residual tumor nodule proved to be of statistical significance in our analysis.

Adult↗
PubMed2001

Radical abdominal hysterectomy.

Radical abdominal hysterectomy and pelvic lymphadenectomy remain the gold standard procedures for the treatment of early cervical cancer. Over the years, the establishment of formal gynecologic oncology training programs, general medical advancements, and new surgical techniques have resulted in a satisfactory tumor resection, with improved overall therapeutic index and reliable cure rates. The role of neoadjuvant and adjuvant therapy continues to be defined as the results from randomized trials emerge.

Female↗
PubMed2001

The benefit of a special elective gynecologic oncology program for obstetrics and gynecology residents.

OBJECTIVE: To assess the benefit of a special elective gynecologic oncology program for Obstetrics and Gynecology (Ob/Gyn) residents. METHODS: We reviewed our housestaff records from July 1992 to June 1998 and the National Residency Matching Program (NRMP) subspeciality match results for gynecologic oncology from its inception in 1994 to 1999. RESULTS: From July 1992 to June 1998, a total of 146 residents participated in our elective program. Of the 104 candidates who went through our program and subsequently participated in the NRMP, 55 (53%) obtained match positions. After completion of the elective, 42 of the 146 residents (29%) did not participate in the NRMP for gynecologic oncology and therefore were not eligible to obtain match appointments. During the study period, there were 255 other residents in the United States who applied for gynecologic oncology fellowship positions through the NRMP and did not participate in our program. Of these 255 candidates, 137 (54%) matched. CONCLUSION: The percentage of residents who went through our program, participated in the NRMP, and obtained fellowships did not differ significantly from the percentage of residents who matched without participating in the program. However, almost one-third of the residents who went through our program did not participate in the NRMP. The reasons for their lack of participation were not formally evaluated, but are likely related to a personal decision to pursue another carrer pathway, a decision facilitiated by their experience in our program. Therefore, it appears that the main benefits of the program are to help potential candidates decide whether or not to pursue a career in gyencologic oncology and to aid fellowship programs in identifying exceptional candidates for subspecialty training.

Fellowships and Scholarships↗
PubMed2000

Effect of adjuvant tamoxifen on the endometrium in women with breast cancer: a prospective study using office endometrial biopsy.

PURPOSE: To determine the frequency of developing abnormal pathologic changes in the endometria of tamoxifen-treated women. To characterize the type of pathologic changes involved. PATIENTS AND METHODS: Between October 1991 and September 1998, 159 patients initiating tamoxifen therapy for breast cancer confined to the breast and axillary lymph nodes were entered in a prospective study. In this study, office endometrial biopsies (EMBs) were obtained during the initiation of tamoxifen and at 6-month intervals for a 2-year period. Three subsequent annual EMBs were recorded for each patient, amounting to a 5-year surveillance. RESULTS: One hundred fifty-nine patients with a median age of 50 years were entered onto study. Patients were assessable if EMBs were performed at least 1 year after the initiation of tamoxifen treatment. Nine patients (5. 7%) were considered protocol violations. The remaining 111 assessable patients underwent a total of 635 EMBs (mean, 5.8 EMBs), with a median surveillance time of 36 months. Eighty-two (12.9%) of the 635 biopsies revealed tissue insufficient for diagnosis. Fourteen patients (12.6%) underwent dilation and curettage (D&C) for an abnormal EMB, persistent bleeding, or for evaluation of adnexal masses at the time of laparoscopy. Findings at D&C included complex hyperplasia (n = 1), abnormal histiocytes (n = 1), simple hyperplasia (n = 2), polyps (n = 4), endocervical polyp (n = 1), and decidualization (n = 2). Three D&Cs were negative. Three patients have undergone hysterectomy. CONCLUSION: EMB was used to monitor the endometrium in the majority (95%) of breast cancer patients on tamoxifen in this trial, but the utility of routine EMB for screening in tamoxifen-treated women seems limited.

Adult↗
PubMed2000

Clinicopathologic features of BRCA-linked and sporadic ovarian cancer.

CONTEXT: Most hereditary ovarian cancers are associated with germline mutations in BRCA1 or BRCA2. Attempts to define the clinical significance of BRCA mutation status in ovarian cancer have produced conflicting results, especially regarding survival. OBJECTIVE: To determine whether hereditary ovarian cancers have distinct clinical and pathological features compared with sporadic (nonhereditary) ovarian cancers. DESIGN AND SETTING: Retrospective cohort study of a consecutive series of 933 ovarian cancers diagnosed and treated at our institution, which is a comprehensive cancer center as designated by the National Cancer Institute, over a 12-year period (December 1986 to August 1998). PATIENTS: The study was restricted to patients of Jewish origin because of the ease of BRCA1 and BRCA2 genotyping in this ethnic group. From the 189 patients who identified themselves as Jewish, 88 hereditary cases were identified with the presence of a germline founder mutation in BRCA1 or BRCA2. The remaining 101 cases from the same series not associated with a BRCA mutation and 2 additional groups (Gynecologic Oncology Group protocols 52 and 111) with ovarian cancer from clinical trials (for the survival analysis) were included for comparison. MAIN OUTCOME MEASURES: Age at diagnosis, surgical stage, histologic cell type and grade, and surgical outcome; and response to chemotherapy and survival for advanced-stage (II and IV) cases. RESULTS: Hereditary cancers were rarely diagnosed before age 40 years and were common after age 60 years, with mean age at diagnosis being significantly younger for BRCA1- vs BRCA2-linked patients (54 vs 62 years; P=.04). Histology, grade, stage, and success of cytoreductive surgery were similar for hereditary and sporadic cases. The hereditary group had a longer disease-free interval following primary chemotherapy in comparison with the nonhereditary group, with a median time to recurrence of 14 months and 7 months, respectively (P<.001). Those with hereditary cancers had improved survival compared with the nonhereditary group (P=.004). For stage III cancers, BRCA mutation status was an independent prognostic variable (P=.03). CONCLUSIONS: Although BRCA-associated hereditary ovarian cancers in this population have surgical and pathological characteristics similar to those of sporadic cancers, advanced-stage hereditary cancer patients survive longer than nonhereditary cancer patients. Age penetrance is greater for BRCA1-linked than for BRCA2-linked cancers in this population.

Adult↗
PubMed2000

The ability of preoperative serum CA-125 to predict optimal primary tumor cytoreduction in stage III epithelial ovarian carcinoma.

PURPOSE: The aim of this study was to determine the ability of preoperative serum CA-125 to predict optimal primary tumor cytoreduction in patients with Stage III epithelial ovarian carcinoma. METHODS: We performed a retrospective chart review of 100 consecutive patients with Stage III ovarian carcinoma who had a serum CA-125 drawn prior to primary cytoreductive surgery. We used a receiver operating characteristic curve to determine the CA-125 level with the maximal prognostic power in predicting optimal versus suboptimal cytoreduction. RESULTS: The median CA-125 level for the 100 patients was 819 U/ml (range 5.6-26,200 U/ml). Optimal cytoreduction (diameter of largest residual tumor nodule < or =1 cm) was obtained in 45 cases (45%). The probability of performing optimal cytoreduction decreased with increasing CA-125 levels. A preoperative CA-125 level of 500 U/ml was identified as the value with the most predictive power. Optimal cytoreduction was achieved in 33 of the 45 cases (73%) with a CA-125 less than 500 U/ml compared to only 12 of the 55 cases (22%) with a CA-125 greater than 500 U/ml. Using a threshold level of 500 U/ml, the preoperative serum CA-125 level was able to predict optimal versus suboptimal cytoreduction with a sensitivity of 78%, specificity of 73%, positive predictive value of 78%, and negative predictive value of 73%. CONCLUSION: The probability of performing optimal cytoreduction in patients with Stage III ovarian carcinoma and a preoperative CA-125 greater than 500 U/ml was approximately one in five. These patients may be candidates for initial laparoscopic evaluation to obtain a confirmatory tissue diagnosis and to determine resectability.

Adult↗
PubMed2000

Analysis of MLH1 and MSH2 expression in ovarian cancer before and after platinum drug-based chemotherapy.

Preclinical studies have demonstrated a relationship between DNA mismatch repair (MMR) status and sensitivity to cisplatin and carboplatin. MMR-deficient cells are resistant to both drugs, and selection for cisplatin resistance in vitro is sometimes accompanied by loss of MMR protein expression. We used immunohistochemical staining techniques to investigate hMLH1 and hMSH2 expression in paired ovarian tumor sections from 54 ovarian cancer patients before and after platinum-based therapy. We sought associations between hMLH1 and hMSH2 protein expression and clinical parameters known to be of prognostic significance as well as response to treatment and overall survival. hMLH1 and hMSH2 staining decreased significantly after platinum-based therapy. The percent of malignant cells that stained positive correlated with the intensity of nuclear staining for both proteins; staining for hMLH1 correlated well with staining for hMSH2. Unexpectedly, expression of nuclear hMLH1 correlated negatively with response to treatment. Expression of nuclear hMLH1 and hMSH2 was positively correlated with pretreatment CA125 level, and expression of nuclear hMSH2 was positively correlated with change in CA125 level after treatment. Tumor stage was associated with expression of nuclear hMSH2, and tumor histological subtype was associated with both hMLH1 and hMSH2 staining. No association was found between expression of either protein and overall survival. These results indicate that the tumor is biologically altered after chemotherapy consistent with treatment-induced selection for cells expressing lower hMLH1 and hMSH2 levels. However, immunohistochemical staining for either hMLH1 or hMSH2 was not highly predictive of drug sensitivity as measured by response or survival.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Ten-year follow-up of ovarian cancer patients after second-look laparotomy with negative findings.

OBJECTIVE: To determine long-term survival and predictors of recurrence in patients with platinum-treated ovarian cancer who were followed for 10 years after second-look laparotomy with negative findings. METHODS: Records were reviewed of 91 consecutive patients with negative findings on second-look laparotomy after platinum-based chemotherapy between January 1978 and January 1987. Statistical analysis used Kaplan-Meier survival curves, Cox proportional hazards, and multiple logistic regression. RESULTS: Mean age of patients was 57 (range 30-79) years. Distribution by stage and grade was as follows: stage I, ten; II, 18; III, 57; IV, six; grade 1, 18; 2, 28; 3, 45. Forty-seven of 91 women had optimal initial cytoreduction. Recurrence-free survival rates for all subjects were 75% at 2 years, 55% at 5 years, and 52% at 10 years. For women with stage I disease, the recurrence-free survival rate was 90% at 2, 5, and 10 years. For women with stage II disease, recurrence-free survival rates were 78, 72, and 66% at 2, 5, and 10 years, respectively. Patients with stage III or IV disease had recurrence-free survival rates of 72, 44, and 40% at 2, 5, and 10 years, respectively. Risk of recurrent disease was related to tumor stage (relative risk [RR] 2.02; 95% confidence interval [CI] 1.2, 3.3; P = .005), grade (RR 2.00; 95% CI 1.3, 3.2; P = .004), and presence of a residual tumor of more than 2 cm at the end of initial surgery (RR 3.19; 95% CI 1.2, 8.5; P = .02). CONCLUSION: Ovarian cancer patients face an appreciable risk of recurrence in the first 5 years after second-look laparotomy with negative findings after platinum-based chemotherapy, but those who remain disease free at 5 years have excellent long-term survival rates. Tumor stage, grade, and presence of a residual tumor of more than 2 cm after initial surgery are significant predictors of recurrence.

Adult↗
PubMed1999

Comparison of standard and CA-125 response criteria in patients with epithelial ovarian cancer treated with platinum or paclitaxel.

PURPOSE: To assess CA-125 as a measure of response in patients treated with paclitaxel. PATIENTS AND METHODS: One hundred forty-four patients treated with paclitaxel derived from four different trials and 625 patients treated with platinum from two trials were analyzed using precisely defined 50% and 75% reductions in CA-125. The standard and CA-125 response rates to paclitaxel and platinum were compared. In addition, we analyzed individual patient groups in which there was a difference in response according to the two response criteria. RESULTS: Patients with stable disease as determined by standard criteria who were treated with platinum and responded according to CA-125 criteria have an improved median progression-free survival compared with patients with stable disease who did not respond according to CA-125 criteria (10.6 v 4.8 months; P<.001). Standard and CA-125 response rates for patients treated with platinum (58.93% v 61.31%, respectively) and paclitaxel (30.65% v 31.67%, respectively) were very similar, as were rates of false-positive prediction of response by CA-125 (platinum 2.2% and paclitaxel 2.9%). Responders to paclitaxel had a significantly improved progression-free survival compared with non-responders by both standard criteria (median progression-free survival, 6.8 v 2.5 months; P<.001) and CA-125 criteria (median progression-free survival, 6.8 v 3.4 months; P<.001). CONCLUSION: Forassessing activity of therapy for ovarian cancer, these data show that precise 50% or 75% CA-125 response criteria are as sensitive as standard response criteria. We propose that they may be used as a measure of response in lieu of or in addition to standard response criteria in clinical trials involving epithelial ovarian cancer. Sensitivity is maintained whether patients are treated with platinum or paclitaxel.

Antineoplastic Agents↗
PubMed1998

Impact of hospital volume on operative mortality for major cancer surgery.

CONTEXT: Hospitals that treat a relatively high volume of patients for selected surgical oncology procedures report lower surgical in-hospital mortality rates than hospitals with a low volume of the procedures, but the reports do not take into account length of stay or adjust for case mix. OBJECTIVE: To determine whether hospital volume was inversely associated with 30-day operative mortality, after adjusting for case mix. DESIGN AND SETTING: Retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database in which the hypothesis was prospectively specified. Surgeons determined in advance the surgical oncology procedures for which the experience of treating a larger volume of patients was most likely to lead to the knowledge or technical expertise that might offset surgical fatalities. PATIENTS: All 5013 patients in the SEER registry aged 65 years or older at cancer diagnosis who underwent pancreatectomy, esophagectomy, pneumonectomy, liver resection, or pelvic exenteration, using incident cancers of the pancreas, esophagus, lung, colon, and rectum, and various genitourinary cancers diagnosed between 1984 and 1993. MAIN OUTCOME MEASURE: Thirty-day mortality in relation to procedure volume, adjusted for comorbidity, patient age, and cancer stage. RESULTS: Higher volume was linked with lower mortality for pancreatectomy (P=.004), esophagectomy (P<.001), liver resection (P=.04), and pelvic exenteration (P=.04), but not for pneumonectomy (P=.32). The most striking results were for esophagectomy, for which the operative mortality rose to 17.3% in low-volume hospitals, compared with 3.4% in high-volume hospitals, and for pancreatectomy, for which the corresponding rates were 12.9% vs 5.8%. Adjustments for case mix and other patient factors did not change the finding that low volume was strongly associated with excess mortality. CONCLUSIONS: These data support the hypothesis that when complex surgical oncologic procedures are provided by surgical teams in hospitals with specialty expertise, mortality rates are lower.

Aged↗
PubMed1998

The role of surgery in the management of ovarian cancer: primary and interval cytoreductive surgery.

Ovarian cancer remains the number one cause of mortality in gynecologic malignancies and the fifth most common cause of death among all malignancies in women. Unfortunately, recent data confirm that only approximately 90% of "apparent" early ovarian cancer are inadequately staged, and only approximately 80% of patients with advanced-stage disease are adequately staged. Interval debulking surgery, a newer treatment modality, appears to have a promising role for patients who cannot be adequately debulked at their initial surgery. Second-look laparotomy continues to be the most accurate way to document responses to chemotherapy in protocol settings, but additional clinical trials with newer second-line chemotherapy will be necessary before definitive statements can be made with regard to survival advantages in patients who undergo second-look laparotomy.

Clinical Trials as Topic↗
PubMed1997

Stage IV ovarian cancer: impact of surgical debulking.

OBJECTIVE: To evaluate the influence of surgical debulking performed on patients with Stage IV ovarian cancer and to determine prognostic factors which identify pts who may benefit from aggressive initial surgical debulking. METHODS: A retrospective chart review was conducted (1/1/87-12/31/93). Eligible patients included all women with FIGO Stage IV ovarian cancer. Clinical information abstracted included age at diagnosis, histology type, tumor grade, criteria for Stage IV classification, surgical procedure performed, and tumor residuum. Optimal surgical status was defined as < or = 2 cm residual disease. Chemotherapy treatment was recorded, as was follow-up. Survival estimates were computed by Kaplan-Meier method with differences in survival calculated by the log-rank test. The Cox proportional hazards regression model was used to identify independent variables which were associated with an improved survival rate. RESULTS: One hundred five women were found in our database with Stage IV ovarian cancer and 97 had complete information available. Median age of the patients was 57 years (range 24-81 years). Papillary-serous histology was found in 55/97 patients (57%) and 50 patients (52%) had grade 3 tumors. Forty-one of 97 patients (42%) had malignant pleural effusion and 20/97 (21%) had liver metastases. Ninety-two patients underwent a primary attempt at surgical debulking and 40/92 were optimally debulked. Twenty-one of 41 patients (51%) with pleural effusion were optimally debulked compared to 20/51 (39%) with other criteria for Stage IV disease (P = NS). Overall median survival was 21 months; optimally debulked patients' median survival was 40 months compared to 18 months for patients with bulky residual disease (P = 0.01). The survival advantage for optimally debulked patients was statistically significant for the two subgroups of patients with and without malignant pleural effusion. In the multivariate analysis only age less than 65 years and optimal debulking were independent predictors of outcome. CONCLUSIONS: Surgical debulking appears to be an important determinant of prognosis in women with Stage IV ovarian cancer, including patients with malignant pleural effusion.

Adult↗
PubMed1997

Comparison of combination therapy with paclitaxel and cisplatin versus cyclophosphamide and cisplatin in patients with suboptimal stage III and stage IV ovarian cancer: a Gynecologic Oncology Group study.

This prospective study compared the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and cisplatin with the standard therapy of cyclophosphamide/cisplatin in women with suboptimal stage III and stage IV ovarian cancer. Of the initial 410 women who presented with advanced disease and greater than 1 cm residual masses after initial surgery, 386 met all eligibility criteria and were randomly assigned to receive a regimen of cisplatin 75 mg/m2 and cyclophosphamide 750 mg/m2 or cisplatin 75 mg/m2 and paclitaxel 135 mg/m2 delivered over 24 hours. Dosage reductions were permitted in the event of significant toxicity. Among 216 patients with measurable disease, responses were reported in 73% of those receiving cisplatin/paclitaxel and in 60% of those receiving cisplatin/cyclophosphamide. Median progression-free survival was significantly longer (P < .001) in the group treated with cisplatin/paclitaxel, compared with those receiving cisplatin/cyclophosphamide (17.9 v 12.9 months, respectively).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Dose escalation of paclitaxel with high-dose carboplatin using peripheral blood progenitor cell support in patients with advanced ovarian cancer.

A phase I study of escalating doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given in combination with high-dose carboplatin was conducted to identify the antitumor efficacy and maximum tolerated dose of paclitaxel in patients who had received sequential cycles of paclitaxel/cyclophosphamide as prior treatment for ovarian carcinoma. Eighteen patients with advanced ovarian cancer were treated in this study. Induction therapy consisted of two cycles of cyclophosphamide 3.0 g/m2 plus high-dose paclitaxel 300 mg/m2 plus filgrastim and leukapheresis to harvest peripheral blood progenitor cells, followed by four courses of rapidly cycled high-dose carboplatin with planned dose escalation of paclitaxel (150, 200, 250, and 300 mg/m2) rescued with peripheral blood progenitor cells. The study was amended after accrual of 11 patients, and the remaining seven patients received a single cycle of induction therapy with paclitaxel/cyclophosphamide, followed by four courses of rapidly cycled high-dose carboplatin with planned dose escalation of paclitaxel through levels 200 and 250 mg/m2. All 18 patients have completed therapy. Of the 15 who are evaluable for response, the pathologic complete response was 33% (five of 15 patients). The administration of escalating doses of paclitaxel in combination with high-dose carboplatin following sequential cycles of paclitaxel/cyclophosphamide induction resulted in significant nonhematopoietic toxicity. Induction with a single cycle of paclitaxel/cyclophosphamide resulted in excellent progenitor cell mobilization, and significantly ameliorated the toxicity of this approach. The response rates thus far obtained are promising and warrant further evaluation.

Adult↗