CA-125 Responses Research Articles

Abstract B47: CBP501, a novel cell cycle dysregulator, in combination with cisplatin (CDDP) and pemetrexed (PM) - results of two phase I/II studies

Abstract Background: CBP501 is a synthetic peptide that appears to increase intracellular CDDP and enhance DNA damage caused by bleomycin and CDDP in cancer cells, which may lead to cell death. Activity has been identified in various tumor models. Previously it was determined that the MTD of single agent CBP501 was 25 mg/m2, with histamine release syndrome (HRS) as the dose limiting toxicity (DLT). Two clinical trials have evaluated CBP501 combinations, determining maximum tolerated dose (MTD), DLT, safety, activity and PK: Study A, phase I, CBP501 with CDDP; Study B, phase I/II, CBP501 with CDDP and PM. Both phase I studies were performed in patients (pts) with solid tumors. The phase II part of Study B is ongoing and will not be presented here. Materials and Methods: Eligibility criteria were standard. CBP501 was given i.v. over 1 hr via central or peripheral catheter, with prophylactic anti-allergics for HRS. MTD was the level below that in which 2 of 3–6 pts had DLT during C1 and C2 for Study A, and C1 for Study B. Study A: q3w, initial CBP501/CDDP doses 3.6/50 mg/m2. Study B: q3w, initial CBP501/CDDP/PM doses 16/75/500 mg/m2. PK is reported separately. Results: The studies were conducted in 3 US centers from Nov-06 to Aug-09. 54 pts were included and treated. Study A) 48 pts in 7 dose levels: M/F 18/30; median age 61 (31–81); PS 0/1: 15/33; median number of prior lines 4 (0–14); primary site: ovarian (14 pts), mesothelioma (MST; 8), NSCLC (5), endometrial (4), prostate (4), other (13); total cycles (cy) administered 182 (median 4, range 1–13). Two DLTs (G3 HRS) occurred at CBP501/CDDP 36.4/75 mg/m2; the MTD was thus defined as 25/75 mg/m2. G3–4 toxicities included fatigue (4 pts), nausea (3), anemia (3), neutropenia (2), HRS (2), vomiting, QTc prolongation and renal failure (1 pt each). HRS was the most common AE, observed in 34 pts (70 %), but did not cause respiratory or hemodynamic problems. Efficacy: 3 confirmed partial responses (PR) were observed (2 platinum-resistant ovarian pts, 1 pleural MST pt); 3 ovarian pts had CA-125 responses. Sustained stable disease (SD) was observed in 5 ovarian pts (10, 9, 7, 5 and 4 cy), 2 pleural MST (13 and 5 cy), 1 neuroendocrine tumor pt (6 cy) and 1 salivary gland adenocarcinoma pt (9 cy). Study B) 6 pts to date, in 2 dose levels (16 and 25 mg/m2 CBP501) with fixed doses of CDDP/PM (75/500 mg/m2/): M/F: 5/1; median age 63 (37–74); PS 0/1: 1/5; primary site: mesothelioma (4 pts), ACUP (1), bladder (1); total cy administered 30 (median 5, range 1–9). No DLTs have been observed; the highest dose studied was defined as the RD for phase II studies. G3–4 related AEs were: DVT (2 pts), anemia (1 pt), syncope (1 pt) and fatigue and anorexia (1 pt). Anemia, fatigue and HRS were the most common AEs, in 6, 5 and 5 pts, respectively. Efficacy: PR was observed in 1 MST pt (9 cy), and SD in 3 MST pts (9, 5 and 4 cy). Conclusion: CBP501 appears to be well tolerated in combination with CDDP and CDDP/PM. The most frequent CBP501 toxicity was HRS, which is manageable. CBP501 did not enhance the expected toxicity of CDDP/PM. PR was seen in platinum-resistant ovarian pts and MST pts. Two randomized phase II studies of CBP501/CDDP/PM are ongoing in pleural MST and NSCLC. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B47.

Phase II Study of Carboplatin, Paclitaxel, and Bevacizumab With Maintenance Bevacizumab As First-Line Chemotherapy for Advanced Müllerian Tumors

PURPOSE New strategies are needed to improve outcomes for patients with advanced ovarian cancer. Bevacizumab is a recombinant humanized monoclonal antibody that neutralizes vascular endothelial growth factor but is associated with GI perforations (GIPs) in patients with recurrent disease. PATIENTS AND METHODS An open-label, phase II clinical trial was conducted in newly diagnosed patients with stage > or = IC epithelial müllerian tumors. Patients received intravenous (IV) carboplatin (area under the curve = 5), paclitaxel (175 mg/m(2) IV), and bevacizumab (15 mg/kg IV) for six to eight cycles on day 1 every 21 days. Bevacizumab was omitted in the first cycle and continued as a single agent for 1 year. Results Sixty-two women participated in this study. Fifty-one patients (82%) were optimally surgically cytoreduced before treatment. The median age was 58 years (range, 18 to 77 years). Forty-five women (73%) had ovarian cancer, 10 (16%) had peritoneal cancer, four (6%) had fallopian tube cancers, and three (5%) had uterine papillary serous tumors. The majority of patients (90%) had stage III or IV disease. A median of 17 maintenance cycles (range, 0 to 25+ cycles) of bevacizumab (556 cycles) were administered with mild toxicity. Treatment was associated with two pulmonary embolisms and two GIPs, all occurring during the chemotherapy phase of treatment (364 total cycles). No grade 4 toxicities were seen during maintenance bevacizumab treatment. Radiographic responses were documented in 21 (75%) of 28 women with measurable disease (11 complete responses and 10 partial responses), with CA-125 responses in 76% of patients (11 complete responses, 21%; and 35 partial responses, 55%). The progression-free survival rate at 36 months was 58%. CONCLUSION The regimen of carboplatin, paclitaxel, and bevacizumab with maintenance bevacizumab is feasible, safe, and worthy of future study in advanced ovarian cancer.

Exploratory analysis of serum CA-125 response to surgery and the risk of relapse in patients with FIGO stage IIIC ovarian cancer

Objective To analyze whether serum CA-125 response to cytoreductive surgery before initiation of postoperative chemotherapy is associated with progression-free survival (PFS) in patients with stage IIIC ovarian carcinoma. Methods We included consecutive patients with paired pre- and postoperative CA-125 measurements who underwent primary cytoreductive surgery followed by platinum-based chemotherapy between 1989 and 2006. The association of perioperative CA-125 changes with PFS was investigated using a time-to-event analysis. A Cox proportional hazards model was fit using clinical, surgical, and postoperative treatment characteristics. Results The study included 307 evaluable patients. Overall, perioperative serum CA-125 changes were associated with PFS. The risk of disease progression increased incrementally as the magnitude of the serum CA-125 response to surgery decreased (trend test; P = 0.003). This association was pronounced in optimally but not observed in suboptimally debulked patients. After optimal cytoreduction, a perioperative increase of serum CA-125 levels was strongly associated with an increased risk of relapse compared to patients who experienced a decline of 80% or more (adjusted HR = 4.2; 95% CI: 2.04–8.66; P = 0.0001). Conclusion Perioperative serum CA-125 changes are strongly associated with the risk of relapse in patients with optimally resected stage IIIC disease. The results of this study provide meaningful support for additional translational research correlating perioperative serum CA-125 responses of patients with molecular tumor characteristics. This may be useful for patient counseling and risk stratification during subsequent clinical trials as well as for the development of novel prognostic models.

Pegylated liposomal doxorubicin (PLD) with bevacizumab (B) in second-line treatment of ovarian cancer (OC): Pharmacokinetics (PK), safety, and preliminary outcome results

5548 Background: PLD activity in platinum-resistant OC is modest. B, with its activity in platinum(Plat)-sensitive and Plat-resistant patients (pts), has not been combined with PLD. PLD intratumoral concentrations, if affected by B, might be reflected in PLD PK. This phase II study of PLD + B was started in 2007 to accrue 48 pts, unless 4 serious (> grade 3) adverse events (AEs) supervened. Methods: Improvement in progression-free survival (PFS) at 6 m from 25 to 40% at 6 m in Plat-resistant OC is primary endpoint. PK of PLD alone at 1h, d 7 and d 21 (cycle 1) vs with B (cycle 2), safety, and response rates (RECIST and CA125 criteria) were secondary endpoints. Dosing: PLD 30 mg/m2 followed by B 15 mg/kg on cycles 2–7 (with option to continue) d 1 every 3 w. Pts recurring within 6 m of platinum-based treatment for OC after < 3 prior regimens (but no PLD or B) were eligible. Exclusions: bowel obstruction, prior perforation, uncontrolled hypertension, or vascular disease. Hematologic, mucocutaneous and renal toxicities were evaluated prior to each cycle, MUGA scans every third cycle; disease status by CA125 and/or RECIST every third cycle. Results: 21 of 24 pts enrolled to date are evaluable. Median age is 65, range 52–83; most had 2 prior chemotherapy regimens. Median 6 (range 3–12) cycles were given with 6 off study with progression at 3–7 cycles. RECIST and CA125 responses are under review; in 11 pts with baseline CA125 of > 40 IU/mL, median increase was 31% by cycle 2; later falling to -57%. AEs did not exceed grade 3; hand-foot syndrome led to PLD dose reduction in 8 pts (33%); asymptomatic decreases in left ventricular ejection fraction (LVEF) >10% in 3 pts were noted, with treatment discontinuation in 1. The mean (±SEM) secondary PK parameter estimates for Cmax, AUC, and elimination half life were 4.5 ± 0.5 ug/mL, 651.7 ± 61 ug/mL x h, and 93.3 ± 19.7 h, respectively. Conclusions: Cycles 1 and 2 PLD PK do not differ. PLD + B is tolerable with PLD dose modifications. Declines in LVEF in 1 institution have uncertain causality. Midway into the trial, safety and time on study encourage completion for study primary endpoint. [Table: see text]

Randomized phase II study of decitabine in combination with carboplatin compared with carboplatin alone in patients with recurrent advanced ovarian cancer

5562 Background: Experimental and clinical data (Gifford et al, Clin Cancer Res. 2004) indicate the potential importance of methylation in mediating resistance to carboplatin in ovarian cancer. A previous phase I trial (Appleton et al, J Clin Oncol. 2007) established the feasibility of combining carboplatin with the demethylating agent decitabine on a day 1 + 8 q4 weekly (w) schedule and PD data provided evidence of target cell demethylation. Methods: Patients (pt) with ovarian cancer relapsing 6–12 months following first line treatment were randomised to receive either 6 cycles of carboplatin AUC 6 q4 w (Arm A), or 90 mg/m2 decitabine as a 6 hour infusion on day 1 and carboplatin AUC 6 on day 8 q4 w (Arm B). The primary endpoint was response rate. An interim analysis was planned after 11 patients were enrolled into Arm B. Results: 29 pt were enrolled. After the first 4 pt had been treated (at 90 mg/m2 decitabine) the frequency of dose delays due to neutropenia was considered unacceptable, and therefore the starting dose of decitabine was reduced to 45 mg/m2 for the subsequent 11 pt. 7 out of 14 pt in Arm A completed 6 cycles compared with 0 of 11 in Arm B (at 45 mg/m2 decitabine). Grade 2/3 hypersensitivity reactions were more common in Arm B than Arm A (64% vs. 21%), as were prolonged treatment delays due to neutropenia (36% vs. 10%). At the interim analysis, in the 11 pt treated with 45mg/m2 (Arm B), there were no RECIST responses, while 2 pt had short-lived CA125 responses (59 and 63 days). In contrast 6 of 14 patients in Arm A had RECIST responses consistent with the expected efficacy of carboplatin in this population. Conclusions: The lack of efficacy, as well as the difficulties in treatment delivery in Arm B, led the project team to conclude that the study should be closed. With this dose and schedule, decitabine is ineffective in reversing carboplatin resistance. Further investigations are ongoing to understand (a) the apparent increased incidence of hypersensitivity and (b) the trend towards reduced efficacy in Arm B. [Table: see text]

Phase II evaluation of CKD-602, a camptothecin analog, administered on a 5-day schedule to patients with platinum-sensitive or -resistant ovarian cancer

Background To evaluate the toxicity and efficacy of a newly developed topoisomerase I inhibitor, CKD-602 in second-line therapy of ovarian cancer. Methods We enrolled 24 patients with recurrent ovarian cancer, of median age 54 years (range, 39–64). Eleven patients had measurable lesions on CT scan, and the other 13 had increased serum CA-125 levels. Eighteen patients had platinum-sensitive disease (minimum treatment free interval ≥ 6 months) and 6 had platinum-resistant disease (minimum treatment free interval < 6 months). CKD-602 (0.5 mg/m 2/day) was administered intravenously for 5 days every 3 weeks. The median number of courses per patient was 6 (range, 1 to 12). Response was evaluated by the evaluation of the size of the mass by CT scan and CA-125 response. Results The overall response rate was 45.0% (9/20), with 4 patients exhibiting partial responses and 5 patients exhibiting 75% CA-125 responses in 20 evaluable patients. Of the 9 responsive patients, 8 were platinum-sensitive (8/15, 53.3%) and 1 was platinum-resistant (1/5, 20.0%). An additional 5 patients showed stable disease, whereas 6 patients exhibited progressive lesions. Of 24 patients, the most common toxicity was hematological, with grades 3 or 4 neutropenia developing in all 24 patients (100%) and in 94 cycles (71.7%). Grade 3 thrombocytopenia developed in 4 patients (16.7%) and 6 cycles (4.6%). None of the patients experienced grades 3 and 4 gastrointestinal toxicities, including nausea, vomiting, and anorexia. Conclusions The newly developed topoisomerase I inhibitor, CKD-602, showed activity against both platinum-sensitive and -resistant ovarian cancer, with acceptable toxicity.

Pazopanib (GW786034) is active in women with advanced epithelial ovarian, fallopian tube and peritoneal cancers: Initial results of a phase II study

5561 Background: Pazopanib is a potent and selective multi-targeted receptor tyrosine kinase inhibitor of VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-a/β, and c-kit that blocks tumor growth &amp; inhibits angiogenesis. Clinical studies have demonstrated activity of anti-angiogenesis agents in ovarian carcinoma. Methods: Pts with epithelial ovarian, fallopian tube or primary peritoneal carcinoma; ECOG PS 0–1 with complete CA-125 response to initial platinum-based chemotherapy with subsequent rise to = 42 U/mL; no disease on CT; or non-bulky disease (masses ≤ 4 cm) were eligible. All pts must have received 1–2 prior regimens. Treatment consisted of pazopanib 800mg QD until PD, withdrawal due to AEs, or withdrawal of consent. Two-stage Green-Dahlberg design was employed requiring 2 CA-125 responses in Stage I (20 pts) to proceed to Stage II (15 pts). Primary endpoint was CA-125 response (= 50% decrease from 2 baseline samples, confirmed ≥ 21 d after initial response sample). Results: Data were available from 15/17 pts enrolled. Median age was 60 yrs (46–79). Majority of pts had platinum-sensitive disease to first line therapy (74%) and had 1 prior line of therapy (60%). 40% of pts relapsed &lt; 6 mos, 27% relapsed 6–12 mos; 27% relapsed &gt; 12 mos. CA-125 responses were seen in 7 pts (47%) with a median time to response of 29 d (5 pts have continuing response of 56–140 d and 2 pts had response duration of 56 &amp; 112 d). SD was observed in 4 pts (27%) and PD in 4 pts (27%). Most common AEs were fatigue, diarrhea, nausea, vomiting, and headache. Most common Gr 3/4 AEs were diarrhea (n=2) and ALT elevation (n=2). Five pts (33%) withdrew due to an AE; 1pt (7%) withdrew due to a potentially disease-related AE (Gr 3 ascites) and 4 pts (26%) withdrew due to toxicity (Gr 3 fatigue, Gr 2 vomiting, Gr 3 double vision, Gr 3 AST/ALT elevations). Conclusions: Preliminary review of Stage I suggests that pazopanib monotherapy demonstrates biologic activity in pts with ovarian cancer with biochemical relapse following prior platinum chemotherapy. The study has met the response criteria to proceed to stage II of enrollment. No significant financial relationships to disclose.

A phase II, open-label study of ispinesib (SB-715992) in patients with platinum/taxane refractory or resistant relapsed ovarian cancer

5562 Background: Kinesin spindle protein (KSP) is required for mitotic spindle bipolarity and cell cycle progression. Ispinesib (ISP), a selective KSP inhibitor, blocks assembly of the mitotic spindle leading to cell cycle arrest and cell death. Methods: This was a phase II study to determine the effectiveness of ISP in patients (pts) with platinum/taxane resistant or refractory ovarian cancer. Pts with progression during, or recurrence &lt; 6 months after prior platinum/taxane therapy, ECOG status 0–2, and CA-125 &gt; 40 U/ml were eligible. ISP was given as a 1 hr IV infusion of 18 mg/m2 Q 21 days. A 2-stage Green-Dahlberg design was employed. In Stage I, 20 evaluable pts were enrolled. If there were no CA-125 responses (Rustin criteria), the study was to be stopped. If &gt; 1 CA-125 responses were seen, 15 more pts were to be enrolled in Stage 2. Overall response was defined by pts who achieved both CA-125 and RECIST criteria. Results: 22 pts with carboplatin/taxane resistant (9) or refractory disease (13) were enrolled: median age = 63 (43–80); 21 were Caucasian; median no. of cycles = 2 (1 - &gt;16). All pts were evaluable for CA-125 assessment. The best CA-125 response was SD in 10 pts (45%); 12 pts had PD (55%). The best radiographic response was a confirmed PR lasting &gt; 30 weeks in one pt who also met CA-125 progression criteria (5%); 5 pts (26%) had SD; and 13 pts (68%) had PD. The most common AEs, in decreasing order, were neutropenia, fatigue, anemia, leukopenia, thrombocytopenia, diarrhea, nausea, vomiting, and decreased appetite. The most frequent Gr 3/4 AE was neutropenia. Conclusions: This study was terminated after Stage I as the CA-125 response criterion to progress to Stage II was not met. One confirmed radiographic partial response was observed. ISP was well tolerated with an acceptable safety profile. No significant financial relationships to disclose.

Topotecan Continuous Infusion: CA-125 Responses Including Patients Pretreated with Other Schedules of Topotecan

Topotecan Continuous Infusion: CA-125 Responses Including Patients Pretreated with Other Schedules of Topotecan

Clinical activity of pertuzumab (rhuMab 2C4) in advanced, refractory or recurrent ovarian cancer (OC), and the role of HER2 activation status

5051 Background: Pertuzumab (P), a humanized HER2 antibody, represents a new class of targeted agents called HER dimerization inhibitors (HDIs) that inhibit dimerization of HER2 with EGFR, HER3 and HER4, and inhibit signaling through MAP and PI3 kinases. A phase I trial has demonstrated safety and activity in several tumors including ovarian cancer (OC). Interim data from a phase II trial with P in OC is presented. Methods: 65 pts with relapsed OC were enrolled with 61 receiving therapy with P. P was administered intravenously with a loading of 840mg followed by 420mg every 3 weeks. Tumor assessments were obtained after 2, 4, 6, 8, 12 and 16 cycles. Response rate (RR) by RECIST was the primary endpoint. Fresh tumor biopsies were mandatory in order to assay for HER2 phosphorylation (pHER2) status. Results: Median age was 59 years (range 35–78) and median ECOG PS was 1 (range 0–3). The median number of prior chemotherapy regimens was 5. 60 pts were evaluable for response. There were 2 objective partial responses (PRs) (RR=3%) and 24 (40%) of pts had stable disease (SD) per RECIST. CA125 RR of >50% reduction was 12%. 11 pts (15%) had SD for >18 weeks (range 18–36 weeks), with 4 pts >32 weeks. Of the 65 tumor biopsies, 31 were evaluable and 8 (26%) were positive for pHER2 by ELISA. Overall median time to progression (TTP) was 6.6 weeks (n=54); TTP for pHER2+ pts was 20.9 weeks (n=8), compared to 5.7 weeks for pHER2- (n=20), and 9.4 weeks for unknown pHER2 status (n=26). P was well tolerated with diarrhea in 57% of pts (grade 1–3). 1 pt had a drop in ejection fraction to < 50% (45%). Conclusions: As a single agent P is well tolerated. Clinical activity was demonstrated by PR’s and CA125 responses in 15%, and SD for > 4 months in 18% of pts with heavily pretreated OC. This study suggests P may be active in OC. Preliminary analysis suggests pHER2 status may be important for P activity. An update on this trial, as well as a 2nd cohort of pts treated with 1050mg single agent P will be reported. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech, Inc. for accrual patient costs only, Genentech

Long term follow-up of patients with recurrent ovarian cancer after Ad p53 gene replacement with SCH 58500.

We have previously reported the safety, efficient gene transfer, and favorable CA125 responses of individuals with recurrent ovarian cancer treated by p53 gene replacement with the adenoviral vector SCH 58500. The purpose of the present investigation was to evaluate the long-term follow-up of these heavily pretreated patients subsequent to SCH 58500 dosing. Patients (n=36) were treated with either single-dose SCH 58500 in the phase I study or with multiple doses (MD) of SCH 58500 over multiple cycles in combination of platinum-based chemotherapy in the phase I/II portion of the study. Five patients were initially treated in the single-dose group and re-enrolled in the MD group. The MD group was evaluated both without the re-enrolled patients as MD1 (n=19), and as MD2 (n=24), which included them. Patients who were only treated on the single-dose arm were designated as SD (n=12). Most patients received additional chemotherapy at the discretion of their physicians on completion of the trial. The current analysis is a retrospective sequential cohort survival analysis. The first patient was treated in March 1997 and the last patient completed SCH 58500 in September 1998. There was no difference in age at diagnosis, Karnofsky performance status, interval between diagnosis to SCH 58500, prior cycles or regimen of chemotherapy, platinum-free interval, percent platinum refractory patients, pretreatment CA125, or largest tumor volume between groups. Both MD groups had a slightly longer chemotherapy-free interval before SCH 58500 than the SD group. Median survival of individuals who received MD SCH 58500 with chemotherapy was 12-13.0 months, compared to only 5 months for those treated with SD SCH 58500. There are 10 long-term survivors more than 20 months after MD treatment for recurrent disease compared to only 2 long-term survivors after SD SCH 58500. The 12- to 13.0-month median survival in a heavily pretreated population with recurrent ovarian cancer compares favorably to the 16-month median survival for individuals treated with paclitaxel at the time of initial recurrence of this disease and is more than double the 5-month survival seen with palliative radiotherapy or paclitaxel failure. These data suggest that further study of SCH58500 is clearly indicated.

Absence of Major Peripheral Neuropathy in a Phase II Trial of Ifosfamide With Vinorelbine in Patients With Ovarian Cancer Previously Treated With Platinum and Paclitaxel

Both ifosfamide and vinorelbine have been shown to produce responses in women with previously treated ovarian cancer. However, vinorelbine has been reported to cause severe neuropathy in patients previously treated with paclitaxel. We assessed a regimen consisting of ifosfamide 1.6 g/m2/d and vinorelbine 30 mg/m2/d for 3 days consecutively every 21 days. Because these doses resulted in severe neutropenia despite the use of granulocyte colony-stimulating factor, doses were reduced to a final level of ifosfamide 960 mg/m2/d and vinorelbine 20 mg/m2/d. Peripheral sensory neuropathy was evaluated by questionnaire. A total of 30 women were treated. All had previously been treated with both a platinum compound and paclitaxel. One partial response was observed among 23 patients with measurable disease, and two CA-125 responses were noted among seven patients without measurable disease. Severe progressive neurotoxicity was not observed. Despite the fact that almost half the patients had not been exposed to cyclophosphamide, this regimen produced few responses. Superior response rates have been reported with single-agent vinorelbine at doses that do not require growth factor support. With this dose and schedule, vinorelbine is reasonably safe therapy for patients who have received prior paclitaxel and who have have mild baseline sensory neuropathy.

A phase II trial of docetaxel in platinum pre-treated patients with advanced epithelial ovarian cancer: A Japanese Cooperative Study

BackgroundThis phase II study was conducted to evaluate the efficacy and toxicity of docetaxel in Japanese patients with advanced ovarian cancer. Patients and methodsDocetaxel was administered at a dose of 70 mg/m2 intravenously to patients with platinum pretreated advanced ovarian cancer. Treatment was repeated every three weeks. No routine corticosteroid premedication was given. ResultsNinety patients with advanced ovarian cancer were entered and sixty were assessable for response. The overall response rate was 28% in the assessable patients (95% confidence interval (95% CI): 17.5%–41.4%). CA125 responses were seen in 8 (24%) of 34 assessable patients for CA125 criteria. The 36 platinum-refractory patients had a response rate of 25% compared with 33% in the platinum-sensitive patients. The predominant toxicity was neutropenia, with 86% of the patients experiencing grade 3 or 4. Hypersensitivity reactions occurred in 37% of the patients and were not life threatening. Edema was mild and infrequent. ConclusionDocetaxel at 70 mg/m2 demonstrated effectiveness as a treatment of both platinum-sensitive and platinum-refractory ovarian cancer patients, with a low incidence of severe hypersensitivity reactions and edema.

Placebo-controlled study on serum concentrations of CA-125 before and after treatment of endometriosis with danazol or high-dose medroxyprogesterone acetate alone or after surgery

Serum concentrations of CA-125 were determined in association with 6-month medical (n = 48) or surgical and medical therapy (n = 40) of endometriosis. The concentration of CA-125 was significantly higher in stages III + IV (66.6 +/- 22.0 [standard deviation] U/ml) than in stage I (20.9 +/- 2.3 U/ml) or II (28.4 +/- 2.8 U/ml); in stage II, the concentration was higher than in stage I. Surgical elimination of endometriosis significantly decreased the level of CA-125, as did danazol, but not medroxyprogesterone acetate (MPA), although these drugs were equal in clinical efficacy. The CA-125 changes during hormonal treatment did not correlate with the clinical response. Postoperatively, CA-125 responses to danazol, MPA, or placebo did not differ significantly from each other. During the 6-month follow-up after medication, the CA-125 concentrations tended to increase, especially in danazol-treated women. The determination of CA-125 is useful in estimating the extent of the disease, but it is less valuable in monitoring the treatment effect. The ability of danazol to suppress CA-125 expression emphasizes the specific properties of this drug.