Predictors of progression free survival, overall survival and early cessation of chemotherapy in women with potentially platinum sensitive (PPS) recurrent ovarian cancer (ROC) starting third or subsequent line(≥3) chemotherapy - The GCIG symptom benefit study (SBS).

BACKGROUND: Potentially platinum sensitive recurrent ovarian cancer (PPS ROC) is defined by a platinum-free interval of >6 months, and usually treated with platinum-based chemotherapy with variable response and benefit in women who have had 3 or more lines of chemotherapy(≥3). We identified baseline characteristics (health-related quality of life[HRQL] and clinicopathological factors), associated with PFS, OS and early progression (within 8 weeks). The goal is to improve patient selection for chemotherapy based on a nomogram predicting PFS. METHODS: HRQL was assessed with EORTC QLQ-C30/QLQ-OV28. Associations with PFS and OS were assessed with Cox proportional hazards regression. Variables significant in univariable analysis were included in multivariable analyses using backward elimination to select those significant. Associations with stopping chemotherapy early were assessed with logistic regression. RESULTS: 378 women were enrolled, with median(m)OS and PFS of 16.6 months and 5.3 months, respectively. The majority had ECOGPS 0-1. Chemotherapy was stopped early in 45/378 participants (12%); with mOS 3.4 months (95% CI: 1.7-7.2). Physical function(PF), role function(RF), cognitive function(CF), social function(SF), Global Health Status(GHS) and abdominal/GI symptoms(AGIS) were significant univariable predictors of PFS(p < 0.030). SF remained significant after adjusting for clinicopathological factors; p = 0.03. PF, RF, CF, SF, GHS and AGIS were significant univariable predictors of OS (p < 0.007); PF, RF, SF and GHS remained significant predictors of OS in multivariable models; p < 0.007. Poor baseline PF and GHS were significant univariable predictors of stopping chemotherapy early (p < 0.007) but neither remained significant after adjusting for clinicopathological factors. CONCLUSION: Baseline HRQL is simple to measure, is predictive of PFS and OS and when used in conjunction with clinicopathological prognostic factors, can assist with clinical decision making and treatment recommendations for women with PPSROC≥3.

A review of sentinel lymph node biopsy for thin melanoma.

INTRODUCTION: Although there is a lack of established survival benefit of sentinel lymph node biopsy (SLNB), this technique has been increasingly applied in the staging of patients with thin (≤1.00 mm) melanoma (T1Nx), without clear supportive evidence. METHODS: We review the guidelines and available literature on the indications and rationale for performing SLNB in thin melanoma. RESULTS: As a consequence of the paucity of evidence of SLNB in thin melanoma, there is considerable variability in the guidelines. It is difficult to define clinicopathologic factors that reliably predict the presence of nodal metastasis. SLNB does not yet inform management in thin melanoma to improve survival outcome. CONCLUSION: Based on available evidence, high risk patients with melanomas between 0.75 and 1.00 mm may be appropriate candidates to be considered for SLN biopsy after discussing the likelihood of finding evidence of nodal progression, the risks of sentinel node biopsy, and the lack of proven survival benefit from any form of surgical nodal staging.

Evaluation of carboplatin dosage based on 4-variable modification of diet in renal disease equation.

BACKGROUND: Traditionally, carboplatin dosage is based on the Calvert formula. Glomerular filtration rate (GFR) and creatinine clearance (CrCl) are often used interchangeably in this formula. The modification of diet in renal disease (MDRD) equation is now routinely available to estimate GFR (eGFR). METHODS: We performed a retrospective analysis of carboplatin dosage in our institute. Calvert formula derived carboplatin dose using eGFR calculated from the MDRD equation was compared to estimated CrCl from the Cockcroft-Gault and Jelliffe equations. RESULTS: Ninety-two carboplatin treatment episodes were recorded. eGFR and CrCl correlated reasonably well with a correlation coefficient (r) of 0.88. The correlation was weakest at lower levels of serum creatinine. Correcting eGFR for body surface area resulted in a tighter correlation (r = 0.94). CONCLUSION: The MDRD derived eGFR is readily available and may prove very useful in calculating carboplatin dosage for patients with impaired renal function.

A randomized phase II trial of SRL172 (Mycobacterium vaccae) +/- low-dose interleukin-2 in the treatment of metastatic malignant melanoma.

We conducted a randomized phase II trial of SRL172 (Mycobacterium vaccae) +/- low-dose interleukin-2 (IL-2) as treatment for stage IV malignant melanoma. The objectives were to establish the safety and efficacy of SRL172 with and without IL-2. All patients had measurable metastatic disease and none received concurrent chemotherapy, radiotherapy, corticosteroids or any other investigational agent. Sixteen patients were randomized into each arm of the trial prior to closure. The trial was halted prematurely when no responses were seen in the first 16 patients receiving SRL172 alone, predicting a response rate of less than 20%. Three partial remissions were seen in the 16 patients receiving SRL172 + IL-2. These patients remained on monthly SRL172 + IL-2, with disease progression at 12, 15 and 23 months. They continued on the trial regimen following surgical management of their disease progression. This trial provides preliminary evidence of a new, non-toxic, immunotherapeutic regimen in the management of malignant melanoma. Further trials are required to establish a definitive response rate and to compare the combination regimen with the regimen of low-dose IL-2 used in this trial. A biological basis for the responses seen in the SRL172 + IL-2 arm also needs to be established.

Odynorgasmia.

Painful ejaculation ("odynorgasmia") is not well recognized. When it occurs it may indicate the precise site of pathology.

Informed consent and randomised controlled trials.

Truly informed consent is a difficult thing to achieve! Patients are not healthy volunteers and their vulnerability challenges their ability to assess the risk/benefit of health choices. In this paper we consider some or the issues surrounding this important aspect of modern practice, and offer some suggestions on how to improve the process, with the goal of increasing participation in clinical research, and enhancing patients' confidence in their medical advisors.

Cytomegalovirus pneumonia in a patient with breast cancer on chemotherapy: case report and review of the literature.

Cytomegalovirus (CMV) pneumonia in the setting of non-transplantation patients is a rarity. We present a case of CMV pneumonitis in a woman with stage IV breast cancer, with brain metastases, receiving both chemotherapy and systemic corticosteroids. A review of the literature reveals this as a unique case. Potential viral etiologies should therefore be considered in cancer patients with pneumonia receiving non-transplantation chemotherapy-regimens, particularly if steroids are a component of their therapy.

New chemotherapy combinations with docetaxel in the treatment of patients with non-small cell lung cancer.

The modest antitumor activity and clinical benefit of conventional platinum-containing multidrug regimens in locally advanced and metastatic non-small cell lung cancer have provided the impetus for the development of novel combinations. The promising single-agent activity of docetaxel makes it an obvious candidate for incorporation into active programs. The Irish Clinical Oncology Research Group is conducting a phase I-II evaluation of a three-drug combination of docetaxel, ifosfamide, and cisplatin with lenograstim support in patients with stages III-IV non-small cell lung cancer. Preliminary results indicate that the regimen is feasible and tolerable up to a maximum tolerated dose level of 3,000 mg/m2 ifosfamide, 75 mg/m2 cisplatin, and 75 mg/ m2 docetaxel. The regimen appears to be quite active, with nine of 12 evaluable patients responding in the phase I component of the trial. This dose level is currently being explored in a phase II trial.

The development of docetaxel (Taxotere) in non-small cell lung cancer--docetaxel in new combinations and new schedules: an overview of ongoing and future developments.

Non-small cell lung cancer is the most common cause of cancer death in the western world. Non-small cell lung cancer is modestly sensitive to chemotherapy with a small survival benefit in locally advanced and metastatic disease. Newer agents such as docetaxel are yielding encouraging response rates both as single agents and in combination. A phase I/II study is in progress in our institution to determine the maximum tolerated dose and noncomparative efficacy of the combination of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France), ifosfamide, and cisplatin, with mesna and lenograstim support, in the treatment of patients with advanced non-small cell lung cancer. To date, nine patients have received 37 cycles of treatment at increasing dose levels (no intrapatient dose escalation). Treatment was administered to patients on an inpatient basis every 3 weeks, with lenograstim on days 3 to 10. Dose-limiting toxicity has not occurred at levels I to III (dose level III: docetaxel 75 mg/m2, cisplatin 75 mg/m2, and ifosfamide 3 g/m2). These preliminary results suggest that the combination of docetaxel, ifosfamide, and cisplatin, with lenograstim support, is well tolerated in the doses evaluated. Preliminary efficacy results show a response rate of 67% (six of nine patients). The study continues to determine the maximum tolerated dose of this regimen in preparation for a phase II evaluation.

Breast cancer and pregnancy.

Sixteen of 194 premenopausal woman with breast cancer developed the disease in association with pregnancy. Eight were pregnant as diagnosis and eight were post-partum. There were significant delays in referral for surgical opinion and treatment among both groups. Two of the eight pregnant patients were diagnosed during the first trimester and one during the second trimester. The rest were at or close to term. Standard surgical therapy without irradiation was employed for early stage disease. Adjuvant chemotherapy posed some problems. One of the patients in the first trimester declined all treatment while the other opted for surgery only until after delivery. There was a favourable obstetrical outcome in all cases and survival for this group of patients is similar to that reported in the medical literature. None of the group had a further pregnancy. The incidence of breast cancer related to pregnancy in this premenopausal group was 8% with 1% occurring in the first trimester. This would mean three or four such cases per annum in Ireland.