Effectiveness of Carboplatin and Paclitaxel as First- and Second-Line Treatment in 61 Patients with Metastatic Melanoma

BACKGROUND: Patients with metastatic melanoma have a very unfavorable prognosis with few therapeutic options. Based on previous promising experiences within a clinical trial involving carboplatin and paclitaxel a series of advanced metastatic melanoma patients were treated with this combination. METHODS: Data of all patients with cutaneous metastatic melanoma treated with carboplatin and paclitaxel (CP) at our institution between October 2005 and December 2007 were retrospectively evaluated. For all patients a once-every-3-weeks dose-intensified regimen was used. Overall and progression free survival were calculated using the method of Kaplan and Meier. Tumour response was evaluated according to RECIST criteria. RESULTS: 61 patients with cutaneous metastatic melanoma were treated with CP. 20 patients (85% M1c) received CP as first-line treatment, 41 patients (90.2% M1c) had received at least one prior systemic therapy for metastatic disease. Main toxicities were myelosuppression, fatigue and peripheral neuropathy. Partial responses were noted in 4.9% of patients, stable disease in 23% of patients. No complete response was observed. Median progression free survival was 10 weeks. Median overall survival was 31 weeks. Response, progression-free and overall survival were equivalent in first- and second-line patients. 60 patients of 61 died after a median follow up of 7 months. Median overall survival differed for patients with controlled disease (PR+SD) (49 weeks) compared to patients with progressive disease (18 weeks). CONCLUSIONS: Among patients with metastatic melanoma a subgroup achieved disease control under CP therapy which may be associated with a survival benefit. This potential advantage has to be weighed against considerable toxicity. Since response rates and survival were not improved in previously untreated patients compared to pretreated patients, CP should thus not be applied as first-line treatment

Combination therapy with docetaxel and S-1 as a first-line treatment in patients with advanced or recurrent gastric cancer: a retrospective analysis

<p>Abstract</p> <p>Background</p> <p>We performed a single-institution retrospective study to evaluate the efficacy and toxicities of combination therapy with docetaxel and S-1 in patients with advanced or recurrent gastric cancer.</p> <p>Methods</p> <p>Eighty-six patients with advanced or recurrent gastric cancer were enrolled. Patients received docetaxel, 40 mg/m², on day 1 and oral S-1, 80 mg/m²/day, on days 1 to 14 every 3 weeks.</p> <p>Results</p> <p>All 84 patients were assessable for response. The overall response rate was 52.4% (44/84) and the disease control rate was 96.4% (81/84). Median time to progression (TTP) and overall survival (OS) were 6.5 (95% CI, 4.8-8.1 months) and 15.1 months (95% CI, 11.7-18.5 months), respectively. The major toxicities were neutropenia, leukopenia, alopecia and anorexia. Grade 3 or 4 hematologic toxicities included neutropenia in 31 patients (36.0%), leukopenia in 27 (31.7%), febrile neutropenia in four (4.7%), and anemia in one (1.2%). Other grade 3 toxicities included anorexia in five patients (5.8%), and stomatitis, diarrhea and nausea in one each (1.2%). There was one treatment-related death (1.2%).</p> <p>Conclusion</p> <p>The combination of docetaxel and S-1 had good clinical activity with acceptable toxicity in patients with advanced or recurrent gastric cancer.</p

Primary ovarian cancer chemotherapy: current standards of care

Chemotherapy has been regarded as standard therapy for the majority of women with advanced epithelial ovarian cancer for several decades, with this role filled largely by the alkylating agents — used as monotherapy — until the mid-1980s. The activity of cisplatin in this disorder was established during the 1970s, and combinations of cisplatin and an alkylating agent were widely used during the late 1980s. However, further research prompted by continuing concerns over poor survival and tolerability led to the adoption of paclitaxel in combination with either cisplatin or carboplatin as first-line therapy in ovarian cancer during the 1990s. Most recent research has focused on further optimisation of these regimens to maximise clinical benefit while minimising toxicity, and investigations into alternative taxanes (e.g. docetaxel), other novel agents and new treatment schedules are ongoing

Phase II trial of docetaxel, cisplatin and fluorouracil followed by carboplatin and radiotherapy in locally advanced oesophageal cancer

This study was performed to assess the efficacy and safety of docetaxel, cisplatin and fluorouracil combination in patients with unresectable locally advanced oesophageal squamous cell carcinoma. Treatment consisted of docetaxel 60 mg m−2, cisplatin 75 mg m−2 on day 1 and fluorouracil 750 mg m−2 day−1 on days 2–5, repeated every 3 weeks for three cycles, followed by carboplatin 100 mg m−2 week−1 for 5 weeks and concurrent radiotherapy (45 Gy in 25 fractions, 5 days week−1). After radiotherapy, eligible patients either underwent an oesophagectomy or received high dose rate endoluminal brachytherapy (HDR-EBT). Thirty-one out of 37 enrolled patients completed the planned chemotherapy and 30 completed chemoradiation. After completion of chemotherapy, 49% (95% CI: 32.2–66.2) had a clinical response. Twelve patients (32%) underwent a resection, which was radical in 60% (postoperative mortality: 0%). A pathological complete response was documented in four patients (11% of enrolled, 30% of resected). The median survival was 10.8 months (95% CI: 8.1–12.4), and the 1- and 2-year survival rates were 35.1 and 18.9%, respectively. Grade 3–4 toxicities were neutropoenia 32%, anaemia 11%, non-neutropoenic infections 18%, diarrhoea 6% and oesophagitis 5%. Nine patients (24%) developed a tracheo-oesophageal fistula during treatment. Even if the addition of docetaxel to cisplatin and 5-fluorouracil (5-FU) seems to be more active than the cisplatin and 5-FU combination, an incremental improvement in survival is not seen, and the toxicity observed in this study population is of concern. In order to improve the prognosis of these patients, new drugs, combinations and strategies with a better therapeutic index need to be identified

Phase II trial of sagopilone, a novel epothilone analog in metastatic melanoma

BackgroundSagopilone is a novel fully synthetic epothilone with promising preclinical activity and a favourable toxicity profile in phase I testing.MethodsA phase II pharmacokinetic and efficacy trial was conducted in patients with metastatic melanoma. Patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate haematological, and organ function, with up to 2 previous chemotherapy and any previous immunotherapy regimens. Sagopilone, 16 mg m⁻², was administered intravenously over 3 h every 21 days until progression or unacceptable toxicity.ResultsThirty-five patients were treated. Sagopilone showed multi-exponential kinetics with a mean terminal half-life of 64 h and a volume of distribution of 4361 l m⁻² indicating extensive tissue/tubulin binding. Only grade 2 or lower toxicity was observed: these included sensory neuropathy (66%), leukopenia (46%), fatigue (34%), and neutropenia (31%). The objective response rate was 11.4% (one confirmed complete response, two confirmed partial responses, and one unconfirmed partial response). Stable disease for at least 12 weeks was seen in an additional eight patients (clinical benefit rate 36.4%).ConclusionSagopilone was well tolerated with mild haematological toxicity and sensory neuropathy. Unlike other epothilones, it shows activity against melanoma even in pretreated patients. Further clinical testing is warranted

Randomised controlled trial comparing single agent paclitaxel vs epidoxorubicin plus paclitaxel in patients with advanced ovarian cancer in early progression after platinum-based chemotherapy: an Italian Collaborative Study from the ‘Mario Negri’ Institute, Milan, G.O.N.O. (Gruppo Oncologico Nord Ovest) group and I.O.R. (Istituto Oncologico Romagnolo) group

The aim of the study was to evaluate the role of epidoxorubicin plus paclitaxel combination (ET) vs single agent paclitaxel (T), as second-line chemotherapy treatment in advanced ovarian cancer patients in early progression within 12 months after platinum-based chemotherapy. From October 1994 up to June 1999, 234 patients from 34 Italian hospitals were randomised to receive: (A) epidoxorubicin (E) 80 mg m(-2) + paclitaxel (T) 175 mg m(-2) (3 h infusion), every 21 days for 4-6 cycles. (B) Paclitaxel 175 mg m(-2) (3 h infusion) every 21 days for 4-6 cycles. Evaluable for survival analysis were 106 and 106 patients in ET and T arm, respectively. Platinum-based monochemotherapy was the first-line treatment in 43% patients, while polichemotherapy containing anthracyclines was the preferred first-line therapy in 22% patients. The median time from the end of first-line therapy to randomisation was 3 months. Treatment was completed in 87 and 85% of T and ET arm, respectively. Haematological toxicity was significantly more common in ET group (ECOG grade 3-4 neutropenia: 37.4% in ET vs 18.2% in T arm). Neuropathies were similar in both arms (sensory: ECOG grade 2-3: 12.1% in ET vs 14.7% in T arm, motor: 6.1% in ET vs 5.3% in T arm). Objective response was achieved in 37.4% of patients in ET group and in 46.9% of patients in T arm. At a median follow-up of time of 48 months, a total of 180 patients progressed and 163 patients died. Survival analysis showed no difference between ET and T (median time to progression: 6 months for both regimens, median survival: 12 and 14 months for ET and T, respectively; hazard ratio for mortality of ET vs T: 1.17 (95% CI 0.86-1.59; P=0.33). The ET regimen does not seem to be more effective than T in refractory advanced ovarian cancer patients in early progression after platinum-based chemotherapy. Despite an acceptable response rate, the control of disease progression remains poor