A randomised, phase II trial of the DNA-hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in combination with carboplatin vs carboplatin alone in patients with recurrent, partially platinum-sensitive ovarian cancer.

BACKGROUND: Our previous laboratory and clinical data suggested that one mechanism underlying the development of platinum resistance in ovarian cancer is the acquisition of DNA methylation. We therefore tested the hypothesis that the DNA hypomethylating agent 5-aza-2'-deoxycytodine (decitabine) can reverse resistance to carboplatin in women with relapsed ovarian cancer. METHODS: Patients progressing 6-12 months after previous platinum therapy were randomised to decitabine on day 1 and carboplatin (AUC 6) on day 8, every 28 days or carboplatin alone. The primary objective was response rate in patients with methylated hMLH1 tumour DNA in plasma. RESULTS: After a pre-defined interim analysis, the study closed due to lack of efficacy and poor treatment deliverability in 15 patients treated with the combination. Responses by GCIG criteria were 9 out of 14 vs 3 out of 15 and by RECIST were 6 out of 13 vs 1 out of 12 for carboplatin and carboplatin/decitabine, respectively. Grade 3/4 neutropenia was more common with the combination (60% vs 15.4%) as was G2/3 carboplatin hypersensitivity (47% vs 21%). CONCLUSIONS: With this schedule, the addition of decitabine appears to reduce rather than increase the efficacy of carboplatin in partially platinum-sensitive ovarian cancer and is difficult to deliver. Patient-selection strategies, different schedules and other demethylating agents should be considered in future combination studies.

Follow-up with CA125 after primary therapy of advanced ovarian cancer has major implications for treatment outcome and trial performances and should not be routinely performed.

BACKGROUND: Only one randomized trial has examined the value of performing routine CA125 measurements during follow-up of ovarian cancer. The results of this trial and implications of frequent CA125 measurements are examined. PATIENTS AND METHODS: The Medical Research Council OV05/European Organisation for Research and Treatment of Cancer 55955 trial enrolled 1442 patients with a CA125 level within the normal range following platinum-based chemotherapy for epithelial ovarian cancer. If CA125 levels rose to more than twice the upper limit of normal, patients were randomized to immediate or delayed chemotherapy. RESULTS: Those randomized in the early arm started chemotherapy a median of 4.8 months earlier than those on the delayed arm. There was no difference in survival between the early and delayed arms. CONCLUSIONS: Women should be advised not to have routine CA125 measurements, providing they are well and have no symptoms suggesting relapse. In asymptomatic patients with a rising CA125 level, chemotherapy can be delayed. Earlier stopping of maintenance therapy just because of rising CA125 might deny patients continuing benefit from that therapy. Use of CA125 to define progression could result in platinum-sensitive patients being falsely classified as platinum resistant.

Phase II trial of combretastatin A4 phosphate, carboplatin, and paclitaxel in patients with platinum-resistant ovarian cancer.

BACKGROUND: A previous dose-escalation trial of the vascular disrupting agent combretastatin A4 phosphate (CA4P) given before carboplatin, paclitaxel, or both showed responses in 7 of 18 patients with relapsed ovarian cancer. PATIENTS AND METHODS: Patients with ovarian cancer that had relapsed and who could start trial therapy within 6 months of their last platinum chemotherapy were given CA4P 63 mg/m(2) minimum 18 h before paclitaxel 175 mg/m(2) and carboplatin AUC (area under the concentration curve) 5, repeated every 3 weeks. RESULTS: Five of the first 18 patients' disease responded, so the study was extended and closed after 44 patients were recruited. Grade ≥2 toxic effects were neutropenia in 75% and thrombocytopenia in 9% of patients (weekly blood counts), tumour pain, fatigue, and neuropathy, with one patient with rapidly reversible ataxia. Hypertension (23% of patients) was controlled by glyceryl trinitrate or prophylactic amlodipine. The response rate by RECIST was 13.5% and by Gynecologic Cancer InterGroup CA 125 criteria 34%. CONCLUSIONS: The addition of CA4P to paclitaxel and carboplatin is well tolerated and appears to produce a higher response rate in this patient population than if the chemotherapy was given without CA4P. A planned randomised trial will test this hypothesis.

Cediranib in addition to chemotherapy for women with relapsed platinum-sensitive ovarian cancer (ICON6): overall survival results of a phase III randomised trial.

BACKGROUND: Cediranib, an oral anti-angiogenic VEGFR 1-3 inhibitor, was studied at a daily dose of 20 mg in combination with platinum-based chemotherapy and as maintenance in a randomised trial in patients with first relapse of 'platinum-sensitive' ovarian cancer and has been shown to improve progression-free survival (PFS). PATIENTS AND METHODS: ICON6 (NCT00532194) was an international three-arm, double-blind, placebo-controlled randomised trial. Between December 2007 and December 2011, 456 women were randomised, using stratification, to receive either chemotherapy with placebo throughout (arm A, reference); chemotherapy with concurrent cediranib, followed by maintenance placebo (arm B, concurrent); or chemotherapy with concurrent cediranib, followed by maintenance cediranib (arm C, maintenance). Due to an enforced redesign of the trial in September 2011, the primary endpoint became PFS between arms A and C which we have previously published, and the overall survival (OS) was defined as a secondary endpoint, which is reported here. RESULTS: After a median follow-up of 25.6 months, strong evidence of an effect of concurrent plus maintenance cediranib on PFS was observed [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.44-0.72, P < 0.0001]. In this final update of the survival analysis, 90% of patients have died. There was a 7.4-month difference in median survival and an HR of 0.86 (95% CI: 0.67-1.11, P = 0.24) in favour of arm C. There was strong evidence of a departure from the assumption of non-proportionality using the Grambsch-Therneau test (P = 0.0031), making the HR difficult to interpret. Consequently, the restricted mean survival time (RMST) was used and the estimated difference over 6 years by the RMST was 4.8 months (95% CI: -0.09 to 9.74 months). CONCLUSIONS: Although a statistically significant difference in time to progression was seen, the enforced curtailment in recruitment meant that the secondary analysis of OS was underpowered. The relative reduction in the risk of death of 14% risk of death was not conventionally statistically significant, but this improvement and the increase in the mean survival time in this analysis suggest that cediranib may have worthwhile activity in the treatment of recurrent ovarian cancer and that further research should be undertaken.

A review of the close surveillance policy for stage I female germ cell tumors of the ovary and other sites.

Ovarian germ cell tumors are rare but very curable at all stages of disease. There is good evidence that surveillance for stage I dysgerminomas is a safe option although many centers worldwide still advocate adjuvant chemotherapy for stage IA nondysgerminomatous tumors, despite the significant risk of developing long-term treatment side effects. Here, we review the safety of our ongoing surveillance program of all stage IA female germ cell tumors. Thirty-seven patients (median age 26, range 14-48 years) with stage I disease were referred to Mount Vernon and Charing Cross Hospitals between 1981 and 2003. Patients underwent surgery and staging followed by intense surveillance, which included regular tumor markers and imaging. The median period of follow-up was 6 years. Relapse rates for stage IA nondysgerminomatous tumors and dysgerminomas were 8 of 22 (36%) and 2 of 9 (22%), respectively, plus one patient with mature teratoma and glial implants also relapsed; 10 of these 11 patients (91%) were successfully cured with platinum-based chemotherapy. Only one patient died from chemoresistant disease. All relapses occurred within 13 months of initial surgery. The overall disease-specific survival of malignant ovarian germ cell tumors was 94%. Over 50% of patients who underwent fertility-sparing surgery went on to have successful pregnancies. We have confirmed again that surveillance of all stage IA ovarian germ cell tumors is very safe and that the outcome is comparable with testicular tumors. We question the need for potentially toxic adjuvant chemotherapy in nondysgerminoma patients who have greater than 90% chance of being salvaged with chemotherapy if they relapse later.

Vascular damaging agents.

To provide a comprehensive overview on vascular targeting agents and the application of radiobiological principles in pre-clinical and clinical studies, we completed a comprehensive review of published medical studies on vascular targeting agents using Pub Med. Vascular targeting agents are now divided into vascular disrupting agents (VDAs), which target the pre-existing tumour vasculature, and angiogenesis inhibitors (AIs), which prevent the formation of new blood vessels. Modest success has been seen when VDAs and AIs are used as single agents and therefore combination therapies that can work in a complimentary and synergistic manner, targeting both the tumour cells and endothelial cells, are needed. Radiobiological principles have been used to increase our understanding of these agents, and can explain the increased efficacy of combination treatments. In particular, the alteration of the tumour microenvironment by AIs and VDAs can lead to enhanced efficacy when combined with chemotherapy or radiotherapy, with phase II/III trials showing encouraging results. The optimal use and scheduling of AIs and VDAs remains to be determined. Further understanding of the mechanisms of action of these potentially very exciting anti-neoplastic agents is urgently required.

Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomised trial.

BACKGROUND: Adjuvant radiotherapy is effective treatment for stage I seminoma, but is associated with a risk of late non-germ-cell cancer and cardiovascular events. After good results in initial studies with one injection of carboplatin, we undertook a large randomised trial to compare the approaches of radiotherapy with chemotherapy in seminoma treatment. METHODS: Between 1996 and 2001, 1477 patients from 70 hospitals in 14 countries were randomly assigned to receive radiotherapy (para-aortic strip or dog-leg field; n=904) or one injection of carboplatin (n=573; dose based on the formula 7x[glomerular filtration rate+25] mg), at two trial centres in the UK and Belgium. The primary outcome measure was the relapse-free rate, with the trial powered to exclude absolute differences in 2-year rates of more than 3%. Analysis was by intention to treat and per protocol. This trial has been assigned the International Standard Randomised Controlled Trial Number ISRCTN27163214. FINDINGS: 885 and 560 patients received radiotherapy and carboplatin, respectively. With a median follow-up of 4 years (IQR 3.0-4.9), relapse-free survival rates for radiotherapy and carboplatin were similar (96.7% [95% CI 95.3-97.7] vs 97.7% [96.0-98.6] at 2 years; 95.9% [94.4-97.1] vs 94.8% [92.5-96.4] at 3 years, respectively; hazard ratio 1.28 [90% CI 0.85-1.93], p=0.32). At 2 years' follow-up, the absolute differences in relapse-free rates (radiotherapy-chemotherapy) were -1.0% (90% CI -2.5 to 0.5) by direct comparison of proportions, and 0.9% (-0.5 to 3.0) by a hazard-ratio-based approach. Patients given carboplatin were less lethargic and less likely to take time off work than those given radiotherapy. New, second primary testicular germ-cell tumours were reported in ten patients allocated irradiation (all after para-aortic strip field) and two allocated carboplatin (5-year event rate 1.96% [95% CI 1.0-3.8] vs 0.54% [0.1-2.1], p=0.04). One seminoma-related death occurred after radiotherapy and none after carboplatin. INTERPRETATION: This trial has shown the non-inferiority of carboplatin to radiotherapy in the treatment of stage I seminoma. Although the absence of disease-related deaths and preliminary data indicating fewer second primary testicular germ-cell tumours favour carboplatin use, these findings need to be confirmed beyond 4 years' follow-up.

Low-risk persistent gestational trophoblastic disease: outcome after initial treatment with low-dose methotrexate and folinic acid from 1992 to 2000.

PURPOSE: We have simplified the treatment of gestational trophoblastic disease (GTD) in order to reduce the number of patients exposed to potentially carcinogenic chemotherapy. Patients who score 0 to 8 on the Charing Cross scoring system are classified as low-risk and receive methotrexate (MTX) and folinic acid (FA), whereas those who score higher than 8 are classified as high-risk and receive the etoposide, methotrexate, and dactinomycin (EMA)/cyclophosphamide and vincristine (CO) regimen. PATIENTS AND METHODS: Between 1992 and 2000, 485 women with GTD were commenced on MTX/FA at Charing Cross Hospital, London, United Kingdom. If patients developed MTX resistance or toxicity, treatment was altered according to the level of beta human chorionic gonadotropin (hCG). If serum hCG was < or = 100 IU/L, patients received dactinomycin; if hCG was greater than 100 IU/L, patients received EMA/CO. RESULTS: The median duration of follow-up was 4.7 years. Overall survival was 100% and the relapse rate was 3.3% (16 of 485 patients). hCG values normalized in 324 (66.8%) of 485 patients with MTX alone, whereas 161 (33.2%) of 485 patients required a change in treatment, 11 because of MTX toxicity and 150 because of MTX resistance. Sixty-seven patients changed to dactinomycin, of whom 58 achieved normal hCG values, and nine required third-line chemotherapy with EMA/CO. hCG values normalized in 93 (98.9%) of 94 patients who changed directly to EMA/CO from MTX. CONCLUSION: Single-agent dactinomycin has activity in patients with low-risk GTD who develop MTX resistance and whose hCG is low. Simplifying the stratification of GTD into two classes (low- and high-risk) does not compromise overall outcome and may reduce the risk of second tumors.

Vascular disrupting agents: a new class of drug in cancer therapy.

AIMS: To provide a comprehensive overview of the current state of development of a novel class of anti-cancer drugs, the vascular disrupting agents (VDAs), previously known as vascular targeting agents (VTAs). MATERIALS AND METHODS: A comprehensive review, analysis and commentary of the published medical literature on VDAs was performed. RESULTS: Tumour vascular targeting therapy exploits known differences between normal and tumour blood vessels. VDAs target the preexisting vessels of tumours (cf anti-angiogenics), and cause vascular shutdown leading to tumour cell death and rapid haemorrhagic necrosis within hours. It is becoming clear that VDAs have overlapping activity with anti-angiogenic drugs, which prevent the formation of new blood vessels. There are two types of VDA. First, biological or ligand-directed VDAs use antibodies, peptides or growth factors to target toxins or pro-coagulants to the tumour endothelium. In contrast, small molecule VDAs work either as tubulin-binding agents or through induction of local cytokine production. VDAs can kill tumour cells resistant to conventional chemotherapy and radiotherapy, and work best on cells in the poorly perfused hypoxic core of tumours, leaving a viable rim of well-perfused tumour tissue at the periphery, which rapidly regrows. Consequently, responses of tumours to VDAs given as single agents have been poor; however, combination therapy with cytotoxic chemotherapy, external-beam radiotherapy, and radioimmunotherapy, which target the peripheral tumour cells, has produced some excellent responses in animal tumours. VDAs are generally well tolerated with different side-effect profiles to current oncological therapies. Dynamic magnetic resonance imaging is most frequently used to obtain a pharmacodynamic end point to determine whether the VDA is acting on its intended target. CONCLUSIONS: VDAs are a promising new class of drug, which offer the attractive possibility of inducing responses in all tumour types with combination therapy.

Epithelial ovarian cancer: a review of current management.

Epithelial ovarian cancer is the most lethal gynaecological cancer among women worldwide, with 6000 new cases diagnosed in the UK each year. Most women present with advanced disease, but, despite a good initial response to treatment, most relapse. The overall 5-year survival rate is 46%, although this drops to about 13% in women with advanced disease. Transvaginal ultrasound and the tumour marker CA125 are being investigated for screening in ongoing randomised trials. Treatment of ovarian cancer is dependent on clinical stage, and should always be managed within a multidisciplinary team. Most cases will require a pelvic clearance and adjuvant chemotherapy. Current guidelines by the National Institute of Clinical Excellence (NICE) recommend that first-line chemotherapy should include a platinum-based regimen with or without paclitaxel. Relapsed ovarian cancer is incurable; however, chemotherapy can improve quality of life and survival. Gene therapy, immunotherapy and signal transduction inhibitors are all potential future therapies, and are being investigated in ongoing clinical research. In this paper we review the literature on the epidemiology, pathology, clinical features and the current treatment options in epithelial ovarian cancer.

Mismanagement of choriocarcinoma due to a false low HCG measurement.

Accurate measurement of HCG is essential for the diagnosis and management of patients with choriocarcinoma. It is therefore important that clinicians are aware of the possible analytical problems associated with the HCG assay if delay in the diagnosis of this curable tumor is to be avoided. We describe the case of a 43-year-old woman with extensive lung metastases who had an unnecessary hysterectomy and lung biopsy and in whom the diagnosis of this potentially rapidly fatal tumor was delayed because of a falsely low HCG level measured by a commercial kit. This underestimation of HCG was due to the 'high dose hook' effect, which is described in detail, and methods for avoiding this analytical problem are described.

The role of CA 125 in epithelial ovarian carcinoma.

CA 125 remains the only tumour marker to have any significant impact on the clinical management of epithelial ovarian carcinoma. Its role has developed over the past two decades by validating CA 125 criteria in large numbers of patients against established methods of disease assessment. CA125 has a role in the work-up of a patient with a pelvic mass. Its role in prognosis and screening remains uncertain. It is of value in the assessment of response to chemotherapy and to identify disease progression. When compared with previous methods of determining the onset of disease recurrence the use of CA 125 has been shown to be more sensitive and to be able to detect it at an earlier stage. However, it remains unknown as to whether the earlier introduction of chemotherapy actually improves survival. Until the results of an MRC / EORTC trial are available regular CA 125 monitoring during follow-up cannot be recommended. Once recurrence is suspected precise criteria based on CA125 can reliably confirm this. With this developing role it is likely that CA 125 will be of even more importance to the management of epithelial ovarian carcinoma in the future.

Lactate dehydrogenase is not a useful marker for relapse in patients on surveillance for stage I germ cell tumours.

As part of surveillance protocols for stage I germ cell tumours, many centres routinely measure human chorionic gonadotrophin (HCG), alpha feto-protein (AFP) as well as lactate dehydrogenase (LDH). In conjunction with regular imaging and clinical examination, does routine measurement of LDH add anything to our relapse/pick up rate? Records of 494 patients at Mount Vernon Hospital who relapsed on surveillance between 1985 and 2005 were examined. Of the 494 patients who relapsed, 125 had raised LDH at the time of relapse. 112 of these had a concurrent rise in either AFP, HCG or both, 11 had their disease detected on CT before the rise in LDH, one had a clinically palpable para-aortic mass and the final patient complained of back pain and his retroperitoneal disease was thus discovered on imaging. Routine measurement of LDH in patients on surveillance for stage I germ cell tumours does not add to the early detection of relapse.

Small cell of the ovary, hypercalcemic type -- analysis of combined experience and recommendation for management. A GCIG study.

UNLABELLED: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare tumor typically affecting young women. It is an aggressive malignancy with a poor prognosis and few long-term survivors. OBJECTIVE: Investigate the outcome of patients with SCCOHT. METHOD: Data were collected for patients with SCCOHT treated in Australia, Canada and Europe. Information included stage, surgery, chemotherapy, radiotherapy, recurrence and survival. RESULTS: The median follow-up is 13 months for all patients and 35.5 months in surviving patients. Ten patients had FIGO stage I tumors, six stage III tumors and one stage unknown. All underwent surgical resection. Adjuvant platinum-based chemotherapy was given to all patients. Seven received adjuvant radiotherapy with either pelvic and para-aortic radiotherapy, average dose 46.5 Gy (40 Gy/25# - 50.4 Gy/23#), or pelvic and whole abdominal radiotherapy, average dose 45 Gy to pelvis and 25 Gy (22.5 Gy/22# - 30 Gy/25#) to abdomen. The median survival for stage I tumors was not reached and was 6 months for stage III tumors. For the ten patients with stage I tumors: six received adjuvant radiotherapy with five alive and disease-free; four received no adjuvant radiotherapy with one alive and disease-free, while three have relapsed with one alive and disease-free after resection. Of the seven patients with stage III or unknown stage tumors, all but one have died. Recurrences were most frequent in the pelvis and the abdomen. Patients receiving salvage treatment with chemotherapy and radiotherapy did poorly. CONCLUSION: We advocate a multi-modality treatment approach including surgery, chemotherapy with the addition of radiotherapy either sequentially or concurrently.

SCOTROC 2A: carboplatin followed by docetaxel or docetaxel-gemcitabine as first-line chemotherapy for ovarian cancer.

The feasibility of sequential carboplatin followed by docetaxel-based therapy for untreated ovarian cancer was determined. Patients received four q3w cycles of carboplatin AUC 7, then four q3w cycles of either docetaxel 100 mg m(-2) (day 1) (arm A); docetaxel 75 mg m(-2) (day 8) and gemcitabine 1250 mg m(-2) (days 1,8) (arm B) or docetaxel 25 mg m(-2) and gemcitabine 800 mg m(-2) (both given weekly (days 1,8,15)) (arm C). A total of 44 patients were randomised to each treatment arm. None of the arms demonstrated an eight cycle completion rate (70.5/72.7/45.5% in arms A/B/C, respectively), which was statistically greater than 60% (P=0.102, P=0.056, P=0.982) which was our formal feasibility criteria, although only the completion rate in arm C was clearly worse than this level. The overall response rate (ORR) after carboplatin was 65.7% in 70 evaluable patients. In evaluable patients, ORRs after docetaxel-based cycles were: arm A 84.0% (21 out of 25); arm B 77.3% (17 out of 22); arm C 69.6% (16 out of 23). At follow-up (median 30 months), median progression-free survival times were: arm A 15.5 months (95% CI: 10.5-20.6); arm B 18.1 months (95% CI: 15.9-20.3); arm C, 13.7 months (95% CI: 12.8-14.6). Neutropenia was the predominant grade 3-4 haematological toxicity: 77.8/85.7/54.4% in arms A/B/C, respectively. Dyspnoea was markedly increased in both gemcitabine-containing arms (P=0.001) but was worse in arm C. Although just failing to rule out eight cycle completion rates less than 60%, within the statistical limitations of these small cohorts, the overall results for arms A and B are encouraging. Larger phase III studies are required to test these combinations.

Effects of platinum/taxane based chemotherapy on acute perfusion in human pelvic tumours measured by dynamic MRI.

Dynamic contrast enhanced MRI (DCE-MRI) is being used increasingly in clinical trials to demonstrate that vascular disruptive and antiangiogenic agents target tumour microcirculation. Significant reductions in DCE-MRI kinetic parameters are seen within 4-24 and 48 h of treatment with vascular disruptive and antiangiogenic agents, respectively. It is important to know whether cytotoxic agents also cause significant acute reductions in these parameters, for reliable interpretation of results. This study investigated changes in transfer constant (K(trans)) and the initial area under the gadolinium curve (IAUGC) following the first dose of chemotherapy in patients with mostly gynaecological tumours. A reproducibility analysis on 20 patients (using two scans performed on consecutive days) was used to determine the significance of DCE-MRI parameter changes 24 h after chemotherapy in 18 patients. In 11 patients who received platinum alone or with a taxane, there were no significant changes in K(trans) or IAUGC in either group or individual patient analyses. When the remaining seven patients (treated with a variety of agents including platinum and taxanes) were included (n=18), there were also no significant changes in K(trans). Therefore, if combination therapy does show changes in DCE-MRI parameters then the effects can be attributed to antivascular therapy rather than chemotherapy.

CA125 in ovarian cancer: European Group on Tumor Markers guidelines for clinical use.

CA125 is currently the most widely used tumor marker for ovarian epithelial cancer. The aim of this article is to provide guidelines for the routine clinical use of CA125 in patients with ovarian cancer. Due to lack of sensitivity for stage I disease and lack of specificity, CA125 is of little value in the detection of early ovarian cancer. At present, therefore, CA125, either alone or in combination with other modalities, cannot be recommended for screening for ovarian cancer in asymptomatic women outside the context of a randomized controlled trial. Preoperative levels in postmenopausal women, however, may aid the differentiation of benign and malignant pelvic masses. Serial levels during chemotherapy for ovarian cancer are useful for assessing response to treatment. Although serial monitoring following initial chemotherapy can lead to the early detection of recurrent disease, the clinical value of this lead-time is unclear. CA125 is the ovarian cancer marker against which new markers for this malignancy should be judged.

A phase II trial of TIP (paclitaxel, ifosfamide and cisplatin) given as second-line (post-BEP) salvage chemotherapy for patients with metastatic germ cell cancer: a medical research council trial.

This phase II trial describes the use of TIP chemotherapy (paclitaxel, ifosfamide and cisplatin) as salvage for patients with metastatic germ cell cancer (GCC) who have failed initial BEP (bleomycin, etoposide and cisplatin) chemotherapy. Patients with first relapse following BEP for metastatic GCC, confirmed by biopsy or sequentially rising markers, received four courses of TIP (paclitaxel 175 mg m(-2) day 1, followed on days 1-5 by ifosfamide 1 g m(-2) intravenously (i.v.) and cisplatin 20 mg2 i.v.) at 3-weekly intervals. The primary outcome measure was response to TIP. In all, 51 patients were registered, of whom 43 were eligible for response assessment. Eight achieved complete remission (CR) and 18 a partial remission with negative markers (PR(-ve)); favourable response rate (FRR = CR + PR(-ve)) 60%, 95% CI (44-75%); survival at 1 year was 70% (56-84%) and failure-free survival 36% (22-50%). In the group of 26 patients meeting the 'good-risk' criteria described by the Memorial Hospital, the FRR was 73% (52-88%) compared with 41% (18-67%) for the 17 'poor-risk' patients. These results are inferior to those previously reported for TIP in a single-centre study when it was given more intensively, at higher dose and with growth factor support. Nonetheless, TIP as described here can cure a substantial proportion of patients.

CA125 response: can it replace the traditional response criteria in ovarian cancer?

CA125 is well established as an accurate and reliable means of monitoring response to treatment and confirming relapse in ovarian cancer patients. Its role in follow-up after initial treatment is less certain and the subject of a current clinical trial. Measuring response with computerized tomography scans is futile in the majority of patients, as disease is often nonmeasurable at presentation, e.g., ascites or peritoneal deposits, or all measurable disease has been removed at the time of surgery. Serial changes in CA125 can be used as a reliable indicator of disease response or progression so that patients can be classified as responding or progressing according to either standard or CA125 criteria. These precise definitions are currently being prospectively validated in conjunction with the new response evaluation criteria in solid tumor response guidelines and are being incorporated into all future clinical trials.