Features of durable response and treatment efficacy for capecitabine monotherapy in advanced breast cancer: real-world evidence from a large single-centre cohort.

PURPOSE: In metastatic breast cancer (MBC) population treated with capecitabine monotherapy, we investigated clinical-pathological features as possible biomarkers for the oncological outcome. METHODS: Retrospective study of consecutive MBC patients treated at University Hospitals Leuven starting capecitabine between 1999 and 2017. The primary endpoint was the durable response (DR), defined as non-progressive disease for > 52 weeks. Other main endpoints were objective response rate (ORR), time to progression (TTP) and overall survival (OS). RESULTS: We included 506 patients; mean age at primary breast cancer diagnosis was 51.2 years; 18.2% had de novo MBC; 98.8% were pre-treated with taxanes and/or anthracycline. DR was reached in 11.6%. Patients with DR, as compared to those without DR, were more likely oestrogen receptor (ER) positive (91.5% vs. 76.8%, p = 0.010) at first diagnosis, had a lower incidence of lymph node (LN) involvement (35.6% vs. 49.9%, p = 0.039) before starting capecitabine, were more likely to present with metastases limited to ≤ 2 involved sites (54.2% vs. 38.5%, p = 0.020) and time from metastasis to start of capecitabine was longer (mean 3.5 vs. 2.7 years, p = 0.020). ORR was 22%. Median TTP and OS were 28 and 58 weeks, respectively. In multivariate analysis (only performed for TTP), ER positivity (hazard ratio (HR) = 0.529, p < 0.0001), HER2 negativity (HR = 0.582, p = 0.024), absence of LN (HR = 0.751, p = 0.008) and liver involvement (HR = 0.746, p = 0.013), older age at capecitabine start (HR = 0.925, p < 0.0001) and younger age at diagnosis of MBC (HR = 0.935, p = 0.001) were significant features of longer TTP. CONCLUSION: Our data display relevant clinical-pathological features associated with DR and TTP in patients receiving capecitabine monotherapy for MBC.

Efficacy of anti-HER2 therapy in metastatic breast cancer by discordance of HER2 expression between primary and metastatic breast cancer.

PURPOSE: In stage IV breast cancer, the efficacy of human epidermal growth factor receptor 2 (HER2) targeted therapies in cases with discordance in HER2 expression between primary and metastatic site is not well known. We studied progression free (PFS) and overall survival (OS) by HER2 concordance when treating women with taxane-trastuzumab (± pertuzumab) in first or second line and trastuzumab-emtansine (T-DM1) or capecitabine-lapatinib in later lines. PATIENTS AND METHODS: Retrospective monocentric study including all breast cancer patients receiving trastuzumab between January 2002 and September 2017 at the University Hospital in Leuven; we selected metastatic patients with an available HER2 status in primary and metastatic site. The Kaplan-Meier method was used for estimating PFS/OS and log-rank test for analyzing between group differences. A Cox model is used for testing difference between groups while correcting for Pertuzumab. Multivariable Cox regression is used to model overall survival as a function group, correcting for possible confounders. RESULTS: We included 74 patients; 46 had an unchanged HER2 status (positive/positive), 9 lost HER2 (positive/negative), while 19 acquired HER2 amplification (negative/positive). 25 out of 28 cases with a discordant HER2 status were positive for ER and/or PgR in the primary site. HER2 positive/negative cases had a significantly lower PFS for taxane-trastuzumab-(pertuzumab) (PFS = 5.5 months), compared to HER2 positive/positive (PFS 9 months, p = 0.01) and HER2 negative/positive (PFS 14 months, p = 0.01) patients. PFS for later line T-DM1 (n = 30) was significantly higher for the HER2 positive/positive group (PFS 6.0 months) than for the discordant groups HER2 negative/positive (PFS 1.0 month, p = 0.04) and HER2 positive/negative (PFS 1.5 month, p = 0.01). After correcting for possible confounders, the HER2 positive/negative group had a significantly worse OS compared to HER2 positive/positive (HR 0.19, 95% CI 0.08-0.44) and negative/positive (HR 0.15, 95% 0.06-0.38). CONCLUSION: Conversion of HER2 status was seen in 28 out of 74 cases and was mostly observed in hormone receptor-positive tumors. In contrast to patients with HER2 loss, patients with a positive conversion of HER2 status derived substantial benefit from first line treatment with taxane-trastuzumab-(pertuzumab). This study highlights the importance of re-biopsying the metastatic lesion and changing treatment according to the last HER2 result.

Palbociclib in highly pretreated metastatic ER-positive HER2-negative breast cancer.

PURPOSE: We aimed to investigate the role of palbociclib, a first-in-class cyclin-dependent kinase 4 and 6 inhibitor, in postmenopausal women with highly pretreated endocrine therapy-resistant metastatic breast cancer (MBC). METHODS: Between 28 September 2015 and 14 March 2017, a compassionate use program was established in the University Hospitals Leuven in which 82 postmenopausal women with estrogen receptor-positive, HER2-negative MBC were included after at least four lines of systemic treatment. The efficacy and safety analysis was performed in 82 patients who had received at least one dose of palbociclib and who had at least 6-month follow-up at the data cut-off point. The primary objective was the evaluation of efficacy of the combination of palbociclib and endocrine therapy with clinical benefit as primary endpoint, defined as the absence of progressive disease and being on treatment for at least 6 months. Secondary objectives were the evaluation of toxicity and the identification of potential predictors for clinical benefit. RESULTS: The median age of the patients was 67.1 years (range 34.8-85.9) at the time of inclusion. The average duration of treatment was 5.6 months (range 1-19), with a median progression-free survival of 3.17 (95% CI 2.76-4.70) months. At the data cut-off point, 10 patients were still on treatment with palbociclib. In this highly pretreated setting, 34 patients experienced no progressive disease within 6 months, resulting in an overall clinical benefit rate (CBR) of 41.5%. 20.7% (17/82) showed stable disease for ≥ 9 months and 13.4% for ≥ 12 months. None of the investigated predicting factors were significantly associated with clinical benefit at 6 months. For 43.9% of the patients, treatment delay or dose reduction was indicated. CONCLUSIONS: Palbociclib in combination with endocrine therapy shows an unexpectedly high CBR and favorable safety profile in heavily pretreated endocrine-resistant estrogen receptor-positive, HER2-negative MBC patients.

Incidence of medication-related osteonecrosis of the jaw in patients treated with both bone resorption inhibitors and vascular endothelial growth factor receptor tyrosine kinase inhibitors.

BACKGROUND: Several case reports and small case series have suggested a higher incidence of medication-related osteonecrosis of the jaw (MRONJ) in patients treated concomitantly with bone resorption inhibitors (BRIs) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs), as compared to patients treated with BRIs alone. We aimed to assess ONJ-incidence in patients exposed concomitantly to BRIs and VEGFR-TKIs. PATIENTS AND METHODS: We reviewed the records of all patients who received VEGFR-TKIs concomitantly with BRIs. Patients, who were treated with BRIs without VEGFR-TKI, served as a control group. Endpoints of the study were total MRONJ-incidence, MRONJ-incidence during the first and second year of exposure, and time-to-ONJ-incidence. RESULTS: Ninety patients were treated concomitantly with BRIs and VEGFR-TKIs with a median BRI-exposure of 5.0 months. Total MRONJ-incidence was 11.1%. During the first year of BRI-exposure (with a median concomitant exposure of 4.0 months), 6 out of 90 patients (6.7%) developed a MRONJ, compared to 1.1% in the control group (odds ratio 5.9; 95%CI 2.0-18.0; p = 0.0035). In Kaplan-Meier estimates, time-to-ONJ-incidence was significantly shorter in patients treated with BRIs and VEGFR-TKIs compared to BRIs alone (hazard ratio 9.5; 95%CI 3.1-29.6; p < 0.0001). MRONJs occurred earlier in patients treated concomitantly compared to patients treated with BRIs only (after a median exposure of 4.5 and 25.0 months, respectively; p = 0.0033). CONCLUSION: With a global MRONJ-incidence of 11%, patients receiving concomitant treatment with VEGFR-TKIs and BRIs have a five to ten times higher risk for development of MRONJ compared to patients treated with BRIs alone.

PET/CT in the staging of patients with a pelvic mass suspicious for ovarian cancer.

OBJECTIVE: To prospectively assess the value of PET/CT for staging, diagnosis and operability of ovarian cancer, with special attention to the peritoneal spread. METHODS: From June 2009 to March 2011, 69 patients with suspicion of having an ovarian cancer underwent an (18)F-FDG PET/CT. To identify the diagnostic value of PET/CT, the results were compared with the findings at diagnostic laparoscopy and/or debulking surgery. RESULTS: There were 56 patients with malignant tumors and 13 with benign tumors. We observed a sensitivity and specificity of 93% and 77%, respectively for malignant tumors with PET/CT. CT alone had a sensitivity and specificity of 96% and 38%, respectively. The overall FIGO classification evaluation for PET/CT and CT were the same. For the evaluation of metastases, the sensitivity of PET/CT was worse, while the specificity was better than CT. Retroperitoneal lymph node metastases were diagnosed better with PET/CT, while there was no difference for peritoneal spread and for the intestines. PET/CT detected another unknown primary tumor in 3 (4.3%) cases. CONCLUSION: PET/CT is better than CT in detecting retroperitoneal lymph node metastases, but not for peritoneal metastases.

Folate receptor alpha (FRA) expression remains unchanged in epithelial ovarian and endometrial cancer after chemotherapy.

OBJECTIVE: Based on its expression profile, folate receptor alpha (FRA) is an attractive candidate for targeted diagnostics and therapeutics. However, applicability of these agents in residual or recurrent disease could be influenced by chemotherapy. We evaluated whether chemotherapy modified FRA expression in non-mucinous epithelial ovarian (EOC) and endometrial carcinoma (EC). METHODS: FRA staining was evaluated by immunohistochemistry, using MAb 26B3, in 81 patients (41 EOCs and 40 ECs) and 17 control tissues (5 benign ovarian cysts, 5 normal ovarian, and 7 normal endometrial tissues). Chemotherapy effect was evaluated in 42 patients (30 paired samples at primary and interval debulking surgery and 12 from primary and recurrent disease). FRA expression was assessed using a semi-quantitative staining algorithm, the M-score (range 0-50). RESULTS: Median difference in M-score between tumor and control samples was 27.5 for EOC (95% CI 10.0 to 45.0) and 6.7 for EC (95% CI -6.7 to 21.7). Paired samples from both primary and interval debulking surgery did not differ in FRA expression in EOC (median difference of M-score between paired samples of 0.0 [95% CI -2.6 to 2.6]). Recurrent EOC tumors reflected FRA status at diagnosis (median difference of M-score between paired samples of 3.3 [95% CI -7.0 to 13.6]). CONCLUSIONS: This study shows no significant difference in FRA expression after chemotherapy, strengthening the rationale for FRA targeted diagnostics and therapeutics in FRA expressing tumors, whether newly diagnosed or at recurrence.

Applying the 2011 St Gallen panel of prognostic markers on a large single hospital cohort of consecutively treated primary operable breast cancers.

BACKGROUND: Many easily measurable and readily available factors are now established as being prognostic in primary operable breast cancer. We here applied the 2011 St Gallen surrogate definition for breast cancer subclassification using tumor grade instead of Ki67. PATIENTS AND METHODS: Four thousand three hundred and eighteen consecutive patients who had surgery for primary operable breast cancer (1 January 2000 and 31 December 2009) in UZ Leuven excluding primary metastastic male breast cancers and those receiving neoadjuvant therapy. Five different surrogate phenotypes were created using the combined expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 together with tumor grade. Disease-free interval (DFI), distant metastastis-free interval (DMFI), locoregional relapse-free interval (LRRFI), breast cancer-specific survival (BCSS) and overall survival (OS) were calculated. RESULTS: Surrogate phenotypes present with significant differences in DFI, DMFI, LRRFI, BCSS and OS. 'Luminal A' tumors presented with the best outcome parameters but the effect weakened at longer follow-up. CONCLUSIONS: The four surrogate markers, agreed upon by the 2011 St Gallen consensus, defined five prognostic surrogate phenotypes in a large series of consecutively treated breast cancer patients. Their prognostic value changed with longer follow-up. The added value of gene expression profile over classical pathological assessment remains to be defined.

Stellate ganglion block for the management of hot flashes and sleep disturbances in breast cancer survivors: an uncontrolled experimental study with 24 weeks of follow-up.

BACKGROUND: We studied the stellate ganglion block (SGB) recently suggested for the treatment of severe vasomotor symptoms and sleep disturbances in breast cancer survivors. Following an initial pilot study, which focused on the acceptability and safety of SGB for this important problem, we evaluated its short- and long-term efficacy. MATERIALS AND METHODS: Postmenopausal breast cancer survivors with severe vasomotor symptoms resistant to standard nonhormonal pharmacological intervention were eligible. Diaries were used to measure daily hot flash scores (frequency and intensity) and sleep quality (Pittsburgh Sleep Quality Index) during scheduled visits at baseline, 1, 4, 12 and 24 weeks following the SGB. Efficacy data were analyzed using longitudinal regression models. RESULTS: Thirty-four patients participated and none refused the SGB procedure. Most patients received more than one SGB. The pilot study found SGB to be safe. In the main study, hot flash scores were reduced from baseline by 64% [95% confidence interval (CI) -74% to -49%] and 47% (95% CI -62% to -27%) at weeks 1 and 24, respectively. The odds ratio of better sleep quality relative to baseline was 3.4 at week 1 (95% CI 1.6-7.2) and 4.3 at week 24 (95% CI 1.9-9.8). CONCLUSION: In the short term, SGB appears to be an effective treatment with acceptable morbidity for some breast cancer survivors with therapy-resistant vasomotor symptoms and/or sleep disturbances. Although sleep quality was maintained out to 24 weeks the efficacy of SGB for hot flashes was reduced over time. A randomized controlled trial is needed to confirm these findings.

Primary retroperitoneal mucinous cystadenocarcinoma: a case report and review of the literature.

A 50-year-old female complained of a painless abdominal distension. Histopathologic examination after cystectomy showed a primary poorly differentiated retroperitoneal mucinous cystadenocarcinoma with a sarcoma-like mural nodule. The patient subsequently underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy, appendectomy, omentectomy and lymphadenectomy. Adjuvant chemotherapy consisted of 6 times carboplatin (AUC 7) in monotherapy (every 4 weeks). Based on 49 cases of primary retroperitoneal mucinous cystadenocarcinoma, we discuss the histogenesis and we define the appropriate treatment.

Prevalent breast cancer patients with a homozygous mutant status for CYP2D6*4: response and biomarkers in tamoxifen users.

Retrospective studies suggest that single nucleotide polymorphisms in the cytochrome P450 2D6 (CYP2D6) gene predict reduced tamoxifen metabolism, better tolerance and worse treatment outcome. We hypothesized that women with this genotype lack tamoxifen-induced endometrial and biochemical changes in follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG). We identified 56 breast cancer patients attending the follow-up clinic with a homozygous mutant (HM) status for the CYP2D6*4 null variant. Here, we report a detailed assessment of tamoxifen activity in 19 CYP2D6 HM women, while they were using tamoxifen either for metastatic (n = 5) or for early disease (n = 14). We assessed response to tamoxifen in metastatic disease. Endometrial appearances and serum levels of FSH and SHBG were assessed from retrospective and prospective testing. Our findings do suggest that the presence of two CYP2D6*4 alleles does not exclude a durable response of tamoxifen in metastatic breast cancer. The transvaginal ultrasonographic appearance of the endometrium in CYP2D6*4/*4 patients on tamoxifen is similar as seen in the normal population of tamoxifen users. The endometrium is increased in thickness with subepithelial cysts and endometrial polyps. Serum levels of FSH and SHBG in CYP2D6*4 HM tamoxifen users were in the range of what would be expected during tamoxifen treatment in the general population. Our findings do show CYP2D6*4/*4 carriers to have activity of tamoxifen on breast cancer, endometrium and serum levels of FSH and SHBG. They support clinical trials prospectively testing the effect of CYP2D6 genetic variability in response to tamoxifen before denying this drug to breast cancer patients only based on their CYP2D6*4 status.

Neoadjuvant chemotherapy followed by interval debulking surgery in patients with serous endometrial cancer with transperitoneal spread (stage IV): a new preferred treatment?

BACKGROUND: To investigate the value of neoadjuvant chemotherapy (NACT), followed by interval debulking surgery (IDS), in endometrial cancer with transperitoneal spread (stage IV). METHODS: Patients with endometrial cancer with transperitoneal spread, as determined by laparoscopy (+/-pleural effusion), were treated with NACT. Efficacy was determined according to the Response Evaluation Criteria in Solid Tumors, residual tumour at IDS and histopathological assessment of tumour regression. RESULTS: A total of 30 patients (median age: 65 years; range:44-81 years) received 3-4 cycles of NACT (83% paclitaxel/carboplatin). Histopathological subtypes were as follows: serous (90%), clear cell (3%) and endometrioid (6%) carcinoma. Response according to RECIST was as follows: 2 (7%) complete remission, 20 (67%) partial remission, 6 (20%) stable disease and 2 (7%) progressive disease (PD). Patients with PD were not operated upon. A total of 24 patients (80%) had optimal cytoreduction (R

Limited clinical benefit from trastuzumab in recurrent endometrial cancer: two case reports.

BACKGROUND: It is hypothesized that the HER-2/neu receptor could be used for targeted therapy in recurrent endometrial cancer. CASES: A patient with type II endometrial cancer (serous), showing strong HER-2/neu overexpression and gene amplification in both primary and recurrent tumor, received single-agent trastuzumab (3x weekly, 8 mg/kg loading, 6 mg/kg maintenance dose). Because of progression after 4 cycles, weekly paclitaxel-trastuzumab (80 mg/m(2) paclitaxel; trastuzumab 4 mg/kg loading, 2 mg/kg maintenance dose) was initiated. However, progressive disease was also noted after 11 weeks of combined treatment. A second patient, with recurrent type II endometrial cancer (grade III endometrioid), had HER-2/neu gene amplification in the primary tumor. However, biopsy from a lung metastasis 3 years later appeared to be HER-2/neu-negative. CONCLUSION: Based on lack of response and changes in tumor biology, trastuzumab was of little clinical value in 2 cases of recurrent type II endometrial cancer. This report underscores the importance of reassessment of a recurrent tumor before initiating targeted treatment.

Timing of debulking surgery in advanced ovarian cancer.

It is clear that primary debulking remains the standard of care within the treatment of advanced ovarian cancer (FIGO stage III and IV). This debulking surgery should be performed by a gynecological oncologist without any residual tumor load, or so-called "optimal debulking." Over the last decades, interest in the use of neoadjuvant chemotherapy together with an interval debulking has increased. Neoadjuvant therapy can be used for patients who are primarily suboptimally debulked due to an extensive tumor load. In this situation, based on the randomized European Organization for Research and Treatment of Cancer-Gynaecological Cancer Group trial, interval debulking by an experienced surgeon improves survival in some patients who did not undergo optimal primary debulking surgery. Based on the GOG 152 data, interval debulking surgery does not seem to be indicated in patients who underwent primarily a maximal surgical effort by a gynecological oncologist. Neoadjuvant chemotherapy can also be used as an alternative to primary debulking. In retrospective analyses, neoadjuvant chemotherapy followed by interval debulking surgery does not seem to worsen prognosis compared to primary debulking surgery followed by chemotherapy. However, we will have to wait for the results of future randomized trials to know whether neoadjuvant chemotherapy followed by interval debulking surgery is a good alternative to primary debulking surgery in stage IIIc and IV patients. Open laparoscopy is probably the most valuable tool for evaluating the operability primarily or at the time of interval debulking surgery.

Age interacts with the expression of steroid and HER-2 receptors in operable invasive breast cancer.

BACKGROUND: The negative association between the oestrogen receptor (ER) and the human epidermal growth factor receptor 2 (HER-2) in breast cancer travels in both directions. ER+ tumours are less likely HER-2+ and HER-2+ tumours are less likely ER+. METHODS: We studied the age-related immunohistochemical (IHC) expression of ER, progesterone receptor (PR) and HER-2 in 2,227 tumours using age as a continuous variable. Steroid receptors were considered positive for any nuclear staining of invasive cancer cells and for HER-2, either for strong expression by IHC (score 3+) or gene amplification by fluorescence in situ hybridisation (FISH). Based on nonparametric regression, the age-related association between steroid receptors and HER-2 was presented as likelihood curves. RESULTS: The association between ER or PR and HER-2 is age-related. The age-related expression of ER and PR is HER-2 dependent. In HER-2(-) cases, the odds ratio (OR) for being ER+ was 2.594 (95% CI = 1.874-3.591) up to age 50 and age-independent thereafter; for PR-expression the OR was 2.687 (95% CI = 1.780-4.057) up to age 45 and 0.847 (95% CI = 0.761-0.942) thereafter. In HER-2+ cases, the OR was 0.806 (95% CI = 0.656-0.991) to be ER+ and 0.722 (95% CI = 0.589-0.886) to be PR+. The age-related OR for breast cancers to be HER-2+ is steroid receptor dependent. Taking together, ER+PR+HER-2+ breast cancers appear on average 5.4 years earlier than breast cancers of any other ER/PR/HER-2 phenotype (95% CI = 3.3-7.5; P < 0.0001). CONCLUSION: There is a qualitative interaction between age and expression of steroid and HER-2 receptors. Our findings suggest a strong age-related selective growth advantage for breast tumour cells belonging to the ER+PR+HER-2+ subgroup.

Clinical study investigating the role of lymphadenectomy, surgical castration and adjuvant hormonal treatment in endometrial stromal sarcoma.

The objective of this study is to assess the therapeutic importance of surgical castration, adjuvant hormonal treatment and lymphadenectomy in endometrial stromal sarcoma (ESS). A retrospective and multicentric search was performed. Clinicopathologic data were retrieved from cases that were confirmed to be ESS after central pathology review. The protocol was approved by the Ethical Committee. ESS was confirmed histopathologically in 34 women, but follow-up data were available in only 31 women. Surgical treatment (n=31) included hysterectomy with or without bilateral salpingo-oophorectomy (BSO) in 23 out of 31 (74%) and 8 out of 31 (26%) cases, respectively. Debulking surgery was performed in 6 out of 31 cases (19%). Stage distribution was as follows: 22 stage I, 4 stage III and 5 stage IV. Women with stage I disease recurred in 4 out of 22 (18%) cases. Among stage I women undergoing hormonal treatment with or without BSO, 3 out of 15 (20%) and 1 out of 7 (14%) relapsed, respectively. Among stages III-IV women receiving adjuvant hormonal treatment or not, 1 out of 5 (20%) and 3 out of 4 (75%) relapsed, respectively (differences=55.0%, 95% CI=-6.8-81.2%). Kaplan-Meier curves show comparable recurrence rates for stage I disease without adjuvant hormonal treatment when compared to stages III-IV disease treated with surgery and adjuvant hormonal treatment. Furthermore, women taking hormones at diagnosis have a better outcome when compared to women not taking hormonal treatment. Three out of 31 (9%) patients had a systematic lymphadenectomy whereas 3 out of 31 (9%) had a lymph node sampling. In one case, obvious nodal disease was encountered at presentation. Isolated retroperitoneal recurrence occurred in 1 out of 31 (3%) of all cases and in 1 out of 8 (13%) recurrences. This single woman later also developed lung and abdominal metastases. Leaving lymph nodes in situ does not appear to alter the clinical outcome of ESS. Although numbers are low, the retrospective data suggest that the need for surgical castration (BSO) in premenopausal women with early-stage disease should be discussed with the patient on an individual basis. The data support the current practice in some centres to administer adjuvant hormonal treatment.

Effectiveness of weekly topotecan in patients with recurrent epithelial ovarian cancer.

The objective of this study was to investigate the effectiveness and toxicity of weekly topotecan in patients with recurrent epithelial ovarian cancer. Twenty patients were treated with topotecan at a dose of 4 mg/m(2) weekly. Efficacy was determined according to the Response Criteria in Solid Tumors (RECIST) Gynecologic Cancer Inter Group criteria. Median age was 62 years (45-78). Patients had received 1-7 (median 3) prior chemotherapy lines. A total of 203 weekly treatments were administered. In 13 patients (65%) treatment delay was necessary due to bone marrow toxicity. Grade 3/4 neutropenia occurred in 11 patients (55%) and grade 3/4 thrombocytopenia in four patients (20%). Six patients (30%) needed a dose reduction, and 42 cycles (21%) were given with dose reduction. No neutropenia, fever, or sepsis was observed. There was one complete response and one partial response (response rate 10%). All patients with response had platin-sensitive disease (three out of eight). Six patients needed blood transfusion. None of the patients required granulocyte/granulocyte-macrophage colony-stimulating factor. The median duration of response was 13 months. In addition, there were four patients (20%) with a stable disease lasting at least for 4 months. Based on the results of this Phase II study, the toxicity of weekly topotecan seems to be lower than with the 3-weekly topotecan. The response rate of 10% is low but was not expected to be higher as these patients were heavily pretreated.