BackgroundThe selection of patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in Castration-Resistant Prostate Cancer (CRPC) patients. Functional polymorphisms within the cytochrome P450 1B1 (CYP1B1) gene have been associated with alterations in enzymatic expression and activity and may change sensitivity to the widely used docetaxel regimen.MethodsCYP1B1 genotyping was performed on blood samples of 60 CRPC patients treated with docetaxel, using TaqMan probes-based assays. Association between CYP1B1-142C>G (leading to the 48ArgGly transition), 4326C>G (432LeuVal), and 4390A>G (453AsnSer) polymorphisms and treatment response, progression-free-survival (PFS) and overall-survival (OS) was estimated using Pearson χ2 test, Kaplan-Meier curves and Log-rank test.ResultsPatients carrying the CYP1B1-432ValVal genotype experienced a significantly lower response-rate (P = 0.014), shorter progression-free-survival (P = 0.032) and overall-survival (P < 0.001). Multivariate analyses and correction for multiple comparisons confirmed its prognostic significance for OS. No significant associations were found among other polymorphisms and both response and clinical outcome.ConclusionsCYP1B1-4326C>G (432LeuVal) polymorphism emerged as possible predictive marker of response and clinical outcome to docetaxel in CRPC patients and may represent a potential new tool for treatment optimization. Larger prospective trials are warranted to validate these findings, which might be applied to the future practice of CRPC treatment.

The study will provide information on patients' quality of life and its variations over time in relation to the treatments received for the prostate cancer.

The results of this study confirm that 153Sm-EDTMP is effective in terms of pain relief and PSA response, with minimal toxicity. When it was administered in combination with chemotherapy, prolonged survival indicated actual clinical benefit, while there were no additive toxicities. These results provide the rationale for future prospective evaluation of combined therapeutic strategies.

Ra alpha therapy is an important therapeutic option for men with CRPC and symptomatic skeletal metastases.

Cytoreductive surgery followed by platinum-and paclitaxel-based chemotherapy represents the standard therapeutic strategy for advanced ovarian cancer (1,2) . Current regimens are able to achieve a clinical complete response in 40-50% and a pathologic complete response only in 25-30% of cases, and moreover, about half of complete responders will subsequently develop recurrent disease. On the basis of these data, there is a major interest to assess the role of consolidation therapies after first-line chemotherapy. On the other hands, more than 80% of patients with advanced ovarian cancer need a second-line treatment for persistent/recurrent disease. Consolidation therapySeveral therapeutic tools have been investigated as consolidation treatments in patients who have obtained a complete or partial response after first-line chemotherapy, but currently available results are contrasting (Table 1).In the experience of the Gruppo Oncologico Nord-Ovest (GONO) (3) including patients in complete response or with minimal residual disease at secondlook, consolidation chemotherapy with induction regimen was associated with a better progression-free survival and overall survival when compared to external radiotherapy.Conversely, Lawton et al. (4) reported that both single-agent chlorambucil and whole abdominal radiotherapy gave unsatisfactory results as consolidation treatment after second-look in patients who were given a cisplatin-based regimen. In the study of Sorbe et al. (5) , 98 patients with stage III ovarian cancer in pathological complete response were randomized to receive whole abdomen radiotherapy vs. six further cycles of induction chemotherapy (cisplatin plus doxorubicin or epirubicin) vs. no consolidation treatment. Progression-free survival was better in radio-therapy arm when compared to both chemotherapy arm (P = 0.048) and control arm (P = 0.039), whereas 5-year overall survival was not significantly different in the three groups. The same authors found that, among 74 patients with microscopic residual disease at second-look, consolidation treatment with either whole abdomen irradiation or chemotherapy obtained similar progression-free and overall survival rates.In a retrospective study including 95 patients with FIGO stage IIB-IV ovarian cancer who achieved pathologic complete response, Favalli et al. (6) found that median survival was better in the 43 patients who received consolidation treatment (consisting in chemotherapy in 35 cases) when compared to the 52 patients who did not (66 months vs. 50 months, P = 0.001).Fiorentino et al. (7) randomly allocated 122 pathologically complete responders to receive further chemotherapy with 5-fluorouracil plus cisplatin vs. no consolidation after second-look.Five-year disease free survival (52% vs. 56%) and 5-year overall survival (70% vs. 63%) were similar in the two groups.Intraperitoneal chemotherapy has a strong pharmacologic and biologic rationale in the therapeutic strategy of ovarian cancer, even if these treatment modalities should be still considered as inv...

The role of nuclear medicine physicians in the multidisciplinary team for the management of patients with prostate cancer has been restricted because of a lack of available tools. The only drugs approved to relieve pain related to bone metastases were β-emitting radiopharmaceuticals. These drugs did not prove to prolong survival when used as single agent and resulted associated with important adverse events. This situation has changed with the introduction of radium 223 because of evidence of improved survival in patients, the good safety profile and the opportunity to avoid clonal selection of tumor cells. Cooperation among physicians involved in cancer management will lead to improvements in the treatment of bone metastases due to prostate cancer and is thought to extend to other tumor types. KeywordsThe management of most prostate cancer cases involves committed specialists such as urologists, medical oncologists, radiotherapists, and nuclear medicine physicians. Evidence shows that in men with high-risk prostate cancer, only a patient-focused program based on a multidisciplinary approach can result in improved survival [1]. The role of nuclear medicine physicians in this multidisciplinary team so far has been restricted to providing pain relief. In castration-resistant prostate cancer (CRPC) patients with bone metastases (mCRPC), radiopharmaceuticals turned out to be useful only for noncurative purposes, exclusively aiming at improving symptomatic pain control. In addition, the available drugs have induced considerable serious adverse events, mostly hematologic, and thus have prevented subsequent therapeutic approaches [2]. Therefore, radionuclide-based therapy for symptomatic bone metastases has remained underused and limited to the late phases of the disease [3].The lack of safe therapeutic approaches to extend survival in CRPC patients has been a challenge for nuclear medicine physicians accustomed to successfully treating other tumor types, such as thyroid tumors with radioiodine therapy, or treating hematologic malignancies with ibritumomab tiuxetan. The recent introduction of the radiopharmaceutical radium Ra 223 (Ra 223) dichloride represents a breakthrough because, for the first time, an impact of a radiopharmaceutical on survival of patients with bone metastases due to prostate cancer was demonstrated in a large Phase III trial [4]. This drug, in fact, received the category 1 recommendation as first-line and second-line option by National Comprehensive Cancer Network (NCCN) guideline similarly to chemotherapy [5], and thus the nuclear medicine physician assumed a key position in the current multidisciplinary team for the treatment of mCRPC. The team should evaluate which patients are suitable for Ra 223 dichloride without limiting access to patients in the terminal stages of the disease and should integrate the nuclear medicine physician into the team with the medical oncologist and surgeon. Future Oncol. (Epub ahead of print)

No abstract

Background. The results of conventional chemotherapy in metastatic colorectal cancer are discouraging, making it a logical target for new treatment approaches a necessary consideration. Suramin is a polysulfonated naphthylurea that binds to several cellular growth factors and has in vitro activity against human colorectal cancer cells. Therefore, this Phase II study of patients with metastatic colorectal cancer was conducted to evaluate its clinical activity. Methods. Suramin was administered as a 6‐day continuous infusion every week for 8 consecutive weeks by using a computer‐assisted dosing of Bayesan pharmacokinetics to maintain suramin plasma concentrations of 200‐250 μg/ml. Twenty patients with metastatic colorectal cancer who were not responsive or in progression within 6 months after completing fluoropyrimidine‐based chemotherapy entered the study. Results. Toxicities included mostly Grade 1 and 2 fatigue, nausea and vomiting, peripheral neurotoxicity, creatinine elevation, and proteinuria. No objective responses were observed, but three of three patients who received 5‐fluorouracil plus folinic acid after suramin achieved a partial response. Conclusions. These results indicate that suramin is inactive in patients with metastatic colorectal cancer pretreated with fluoropyrimidines. Pretreatment with suramin may have changed the biology of the tumor, sensitizing it to fluoropyrimidines. Studies to investigate this possibility are in progress. Cancer 1995;75:440‐3.