GAMEC--a new intensive protocol for untreated poor prognosis and relapsed or refractory germ cell tumours.

There is no consensus as to the management of untreated poor prognosis or relapsed/refractory germ cell tumours. We have studied an intensive cisplatin-based regimen that incorporates high-dose methotrexate (HD MTX) and actinomycin-D and etoposide every 14 days (GAMEC). Sixty-two patients were enrolled in a phase 2 study including 27 who were untreated (IGCCCG, poor prognosis) and 35 with progression despite conventional platinum based chemotherapy. The pharmacokinetics of the drugs were correlated with standard outcome measures. Twenty of the untreated patients were progression free following GAMEC and appropriate surgery, as were 18 individuals in the pretreated group. None of the established prognostic factors for therapy for pretreated patients could identify a poor-prognosis group. Five out of nine late relapses to prior chemotherapy were progression free following GAMEC and appropriate surgery. All patients had at least one episode of febrile neutropenia and there were five (8%) treatment-related deaths. PK values were not predictive of efficacy or toxicity, although the dose intensity in the pretreated group of patients, especially of HD MTX, was significantly correlated with progression-free survival (PFS). GAMEC is a novel intensive regimen for this group of patients producing encouraging responses, although with significant toxicity. For those in whom it fails, further therapy is still possible with durable responses being seen.

Peyronie's disease with erectile dysfunction: penile modeling over inflatable penile prostheses.

OBJECTIVES: To evaluate, retrospectively, the impact of penile correction by modeling of the penis over an inflatable penile prosthesis and the subsequent improvement in erectile function. Advanced Peyronie's disease with severe penile curvature and poor quality erections presents a challenge to the urologist. METHODS: In our series, 46 patients with advanced Peyronie's disease and associated erectile dysfunction underwent insertion of an inflatable penile prosthesis between 1998 and 2003. Of the 46 patients, 28 (61%) underwent a standard modeling procedure; the other 18 patients (39%) did not need additional modeling, because their curvature was corrected by inflation of the prosthesis alone. Patients were evaluated postoperatively in the clinic, as well as by a postal questionnaire. RESULTS: Of the 46 patients, 44 were satisfied with the penile correction and 2 (4.4%) underwent removal of their prosthesis because of infection. These 2 patients underwent revision surgery; subsequently both prostheses had to be removed, one for severe pain and the other for urethral erosion. None of the patients underwent reoperation for additional straightening. Of the 44 patients with intact prostheses, erectile function significantly improved in 41 (93%). CONCLUSIONS: The results of our study have indicated that patients with severe Peyronie's disease and erectile dysfunction should be offered the choice of penile modeling over an inflatable penile implant to correct the curvature, as well as improve erectile function.

Carboplatin AUC8 in combination with etoposide and bleomycin in the treatment of intermediate and poor-risk metastatic germ cell tumours: a phase II study.

PURPOSE: Carboplatin has demonstrated significantly poorer response rates in non-seminomatous germ cell tumours. A phase II study of higher than standard doses of carboplatin was conducted because of suspicion that the poorer response might have been due to suboptimal dosing. PATIENTS AND METHODS: A group of 19 patients with advanced germ cell tumours (International Germ Cell Cancer Collaborative Group intermediate and poor prognosis) were treated with carboplatin at an AUC of 8 mg/ml.min (using Calvert's formula) on day 1, etoposide 120 mg/m2 days 1-3 and bleomycin 60,000 U over 2 days (EBCa). Treatment was repeated every 3 weeks and a maximum of four courses was given. RESULTS: Of the 19 patients, 7 (37%) achieved complete remission, of whom 6 (32%) remained long-term progression-free. Post-chemotherapy surgery and further chemotherapy salvaged an additional 26%, leading to an overall disease-free survival rate of 58%. No relationship between outcome and degree of myelosuppression could be established. CONCLUSION: Dose-escalated carboplatin in combination, although feasible, did not improve the results and led to poorer results than those expected with cisplatin-based therapy. There is no evidence that the patients relapsing following this were easier to salvage. Further investigation of this regimen cannot be recommended.