Second-line chemotherapy of metastatic malignant melanoma with intravenous treosulfan: a phase II multicentre trial

The purpose of this multicentre phase II trial was to evaluate time to progression, survival time, rate of objective tumour response and toxicity of second-line intravenous treosulfan chemotherapy in stage IV melanoma patients. Thirty-one patients with measurable stage IV malignant melanoma and prior chemotherapy with a dacarbazine-containing regimen were included. Of this group, 26 patients were evaluable. All patients received treosulfan (8 g/m intravenously on day 1; cycle repeated every 28 days up to six courses). Patients were evaluated for tumour response, survival time and toxicity. No objective responses (complete or partial) were observed. Five patients (19%) showed no change and 21 had progressive disease after treosulfan treatment. Four patients experienced a minor or mixed response. The median time to progression was 1.8 months (95% confidence interval [CI] 1.6-2.1 months) and the median overall survival was 6.5 months (95% CI 3.1-10 months). The 1 year survival rate was 33.9% (95% CI 15.4-52.3%). Leukocytopenia and thrombocytopenia (Common Toxicity Criteria grades 3 and 4) occurred in 15% and 18% of cases, respectively. The non-haematological toxicity of this outpatient regimen was mild. In conclusion, intravenous treosulfan treatment does not induce objective response rates when used as a second-line treatment of metastatic malignant melanoma.     

Vindesine for metastatic malignant melanoma. A phase II trial

Sixteen patients, 13 of whom had received prior chemotherapy, were treated with vindesine for advanced malignant melanoma. Previous treatment included vinca alkaloids in six. Thirteen patients received vindesine, 4 mg/m2 and three received vindesine, 3 mg/m2 by weekly I.V. injection. There were two partial (12%) and no complete responses among all of the patients. Both responses occurred in subcutaneous lesions and lasted for 4 and 6 weeks, respectively. Fifteen patients could be evaluated for treatment-related toxicity. The most common side effect was modest leukopenia (less than 3000/microliter) in 10 patients (67%). The lowest leukocyte count recorded was 1100/microliter. Thrombocytopenia was not encountered. Neurotoxicity, manifest most commonly as mild or moderate peripheral paresthesiae, was seen in eight patients (53%).     

A phase II trial of taxol in metastatic melanoma

Taxol is an investigational new drug which is currently undergoing Phase II evaluation in various tumors. It is a plant alkaloid extracted from the western Yew, Taxus brevifolia. In this study, patients with metastatic melanoma who were previously untreated, received Taxol at a starting dose of 250 mg/m2 delivered as a continuous intravenous (IV) infusion over 24 hours, at 3-week intervals. All patients were premedicated with oral dexamethasone and IV diphenhydramine hydrochloride as prophylaxis against allergic reactions. Three of 25 patients had a partial response (PR) for a response rate of 12% (CI, 3%-31%). In addition four patients had objective regression of tumor that failed to qualify for a PR but these responses were as durable, lasting 6 to 17 months. No patient experienced acute allergic reactions. The major toxicity of Taxol was neutropenia requiring dose reduction to 200 mg/m2 in a majority of the patients. Our data confirm that Taxol has definite although limited activity against metastatic melanoma.     

Sequential biochemotherapy versus chemotherapy for metastatic melanoma: results from a phase III randomized trial.

PURPOSE: The addition of cytokines to chemotherapy has produced encouraging results in advanced melanoma. In this phase III trial, we compared the effects of chemotherapy (cisplatin, vinblastine, and dacarbazine [CVD]) with those of sequential biochemotherapy consisting of CVD plus interleukin-2 and interferon alfa-2b. PATIENTS AND METHODS: Metastatic melanoma patients who had not previously received chemotherapy were stratified by prognostic factors and given chemotherapy or biochemotherapy. CVD consisted of dacarbazine (days 1 and 22) and cisplatin and vinblastine (days 1 to 4 and 22 to 25). Biochemotherapy involved CVD with vinblastine reduced 25% plus interleukin-2 by 24-hour continuous infusion (on days 5 to 8, 17 to 20, and 26 to 29) and interferon alfa-2b by subcutaneous injection (on days 5 to 9, 17 to 21, and 26 to 30). Response was assessed every 6 weeks. RESULTS: Among 190 patients enrolled, 91 were assessable for biochemotherapy and 92 for chemotherapy. Ten percent of the patients were alive a median of 52 months from start of therapy. Response rates were 48% for biochemotherapy and 25% for chemotherapy (P =.001); six patients given biochemotherapy and two given chemotherapy had complete responses. Median time to progression (TTP) was 4.9 months for biochemotherapy and 2.4 months for chemotherapy (P =.008); median survival was 11.9 and 9.2 months, respectively (P =.06). The influence of treatment on TTP and survival was confirmed in multivariate analyses with other prognostic factors not included in the original stratification. Biochemotherapy produced substantially more constitutional, hemodynamic, and myelosuppressive toxic effects. CONCLUSION: Cytokines substantially augment the antitumor activity of chemotherapy at the expense of considerable toxicity in patients with metastatic melanoma.     

Temozolomide in combination with cisplatin in patients with metastatic melanoma: a phase II trial

The present study was designed to assess the efficacy and safety of combination therapy with temozolomide plus cisplatin in patients with metastatic melanoma. Thirty patients with metastatic melanoma were enrolled. Treatment consisted of intravenous cisplatin (75 mg/m) on day 1 and oral temozolomide (200 mg/m) on days 1 to 5, every 4 weeks. Nine patients (30.0%) achieved an objective response, including two complete (6.7%) and seven partial (23.3%) responses. The median response duration was 161 days. The median progression-free and overall survival times were 72 and 120 days, respectively. Myelosuppression and emesis were the primary toxicities. In conclusion, temozolomide combined with cisplatin is an active and safe first-line chemotherapy regimen with acceptable and easily manageable toxicities in patients with metastatic melanoma.     

CCI-779 in metastatic melanoma: a phase II trial of the California Cancer Consortium

BACKGROUND: CCI-779 is an analog of the immunosuppressive agent, rapamycin, that has demonstrated activity against melanoma in preclinical models and shown clinical benefit in patients with breast and renal carcinoma. CCI-779 is not immunosuppressive when administered on an intermittent schedule, and its toxicity is modest, consisting of nausea, diarrhea, hypertriglyceridemia, thrombocytopenia, asthenia, and follicular dermatitis. METHODS: The current trial was designed to detect a median time to disease progression of >18 weeks in patients with metastatic melanoma treated with a 250-mg weekly dose of CCI-779 administered intravenously after diphenhydramine premedication. Patients with measurable disease, no more than one previous chemotherapy regimen for metastatic disease, and normal organ function were eligible, and patients with central nervous system involvement, P450-inducing or P450-suppressing drugs, or hypertriglyceridemia were excluded. RESULTS: Thirty-three patients (21 males) were treated, 21 of whom had been treated previously with chemotherapy and/or biologic agents for advanced-stage disease. One patient had a partial response lasting 2 months. The median time to disease progression and overall survival were 10 weeks and 5 months, respectively. Toxicity was mild and predominantly mucocutaneous (stomatitis, diarrhea, and rash). Hyperlipidemia was cumulative and was managed with lipid-lowering agents. CONCLUSIONS: CCI-779 was not sufficiently active in melanoma to warrant further testing as a single agent.     

A phase II trial of arsenic trioxide in patients with metastatic melanoma

BACKGROUND: Arsenic trioxide induces growth inhibition and apoptosis in human melanoma cell lines. Therefore, a Phase II trial was conducted to evaluate the efficacy and toxicity of single-agent arsenic trioxide in patients with Stage IV melanoma. METHODS: Twenty patients, 10 with metastatic melanoma of cutaneous origin and 10 with metastatic melanoma of choroidal origin, received arsenic trioxide 0.25 mg/kg/day for 5 days, followed by a maintenance dose of 0.35 mg/kg/day twice a week. All patients with melanoma of cutaneous origin and four patients with melanoma of choroidal origin had received prior therapy. RESULTS: Single-agent arsenic trioxide did not induce clinical response in this patient population. Eight patients (five with melanoma of cutaneous origin, and three with melanoma of choroidal origin) had disease stabilization for at least six weeks. The median overall survival duration for patients with melanoma of cutaneous origin was 7.9 months, and that of patients with melanoma of choroidal origin has not been reached at a median follow-up duration of 11.8 months. Grade 3 toxicity included neutropenia, fatigue, abdominal pain, and arthralgia. Grade 4 toxicity did not occur. CONCLUSIONS: Single-agent arsenic trioxide was generally well tolerated; however, no tumor regression was observed in this patient population. Future clinical trials should evaluate arsenic trioxide in combination with other anticancer drugs that may improve its clinical activity in melanoma.     

Improving outcome of chemotherapy of metastatic breast cancer by docosahexaenoic acid: a phase II trial

Background:

Breast cancer becomes lethal when visceral metastases develop. At this stage, anti-cancer treatments aim at relieving symptoms and delaying death without resulting in additional toxicity. On the basis of their differential anti-oxidant defence level, tumour cells can be made more sensitive to chemotherapy than non-tumour cells when membrane lipids are enriched with docosahexaenoic acid (DHA), a peroxidisable and oxidative-stress-inducing lipid of marine origin.

Methods:

This open-label single-arm phase II study evaluated the safety and efficacy (response rate), as primary end points, of the addition of 1.8 g DHA daily to an anthracycline-based chemotherapy (FEC) regimen in breast cancer patients (n=25) with rapidly progressing visceral metastases. The secondary end points were time to progression (TTP) and overall survival (OS).

Results:

The objective response rate was 44%. With a mean follow-up time of 31 months (range 2–96 months), the median TTP was 6 months. Median OS was 22 months and reached 34 months in the sub-population of patients (n=12) with the highest plasma DHA incorporation. The most common grade 3 or 4 toxicity was neutropaenia (80%).

Conclusion:

DHA during chemotherapy was devoid of adverse side effects and can improve the outcome of chemotherapy when highly incorporated. DHA has a potential to specifically chemosensitise tumours.     

A phase II study of cisplatinum and continuous infusion 5-fluorouracil for metastatic melanoma.

Advanced or metastatic melanoma responds poorly to chemotherapy, which has no impact on survival. Responses have been recorded using cisplatinum as a single agent. This study tested the established combination of cisplatinum 100 mg/m2 and 5-fluorouracil 1 g/m2/day continuously intravenously for 5 days repeated every 3 weeks in patients with disseminated melanoma. Twenty-nine patients, 13 having received no prior systemic chemotherapy, received 49 cycles of therapy (median 1, range 1-4). Only one previously untreated patient achieved a partial response with a failure-free survival of 6.5 months and an overall survival of 7.7 months from the commencement of therapy. The major toxicities were nausea and vomiting, (grade 3 in eight patients), stomatitis (grade 4 in two patients, grade 3 in two patients), and myelosuppression. The study showed that cisplatin and 5-fluorouracil have a low order of activity in patients with advanced or disseminated melanoma.     

Granulocyte-macrophage colony-stimulating factor alone or with dacarbazine in metastatic melanoma: a randomized phase II trial.

The potential antitumoral effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) led us to evaluate GM-CSF alone or with dacarbazine (DTIC) in metastatic melanoma in first line randomized phase II. Treatment was arm A: GM-CSF: 5 microg kg(-1), bid, 14 consecutive days every 21 days and arm B: GM-CSF: 5 microg kg(-1), bid, day 2 to day 19 every 21 days and DTIC: 800 mg m(-2), day 1 of each cycle. 32 patients (pts) were included, 15 pts in arm A and 17 in arm B. All pts had visceral metastatic sites. 9 had only one metastatic site. The median number of cycles given was 2 in arm A and 3 in arm B. 100% and 89.4% of the planned dose of GM-CSF was given in arm A and arm B respectively. No objective response was obtained. 19 pts experienced at least WHO grade 3 toxicity. All pts had fever, 29 had a decrease in performance status and 23 had pain. Grade 3 toxicity were fever (38.7%), decrease in performance status (32.3%), pain (19.4%) and dyspnoea (12.5%). In this study, GM-CSF alone or in association with DTIC did not induce any antitumoral activity with subsequent toxicity.     

Outpatient combination chemoimmunotherapy for patients with metastatic melanoma. Results of a phase I/II trial

BACKGROUND: Few studies have examined the feasibility, safety, and efficacy of an outpatient biochemotherapy regimen of low dose, subcutaneously administered interleukin-2 (IL-2) for patients with metastatic (Stage IV) melanoma. METHODS: Nineteen patients were treated with intravenous cisplatin and dacarbazine (DTIC), oral tamoxifen, and subcutaneous IL-2 and interferon-alpha-2b (IFN). Eligibility requirements included bidimensionally measurable metastatic melanoma, a Karnofsky performance score of 60 or higher, absence of significant cardiac or pulmonary dysfunction, no prior DTIC or cisplatin chemotherapy, and no evidence of central nervous system involvement. Patients were given a minimum of 2 6-week cycles. Treatment was continued in the absence of progressive disease, and patients were monitored for response at two-cycle intervals. RESULTS: Of the 19 patients, 1 (5%) achieved a complete response; 6 (32%) a partial response; 3 (16%) stable disease; and 9 (47%) progressive disease, for an overall response proportion of 37% (95% confidence interval, 16-61%). The median survival of the treated cohort was 10.6 months. The mean time to disease progression for patients with stable disease or better was 8.4 months, with a mean response duration of 5.1 months. The most common toxicities noted were constitutional symptoms, weight loss, nausea, neutropenia, and fatigue. The 19 patients received a total of 59 cycles of treatment, and IL-2, IFN, or both were held in 14 of these cycles secondary to Grade 3 or 4 toxicities. In addition, six patients required dose reduction of IL-2 and/or IFN. CONCLUSIONS: Chemoimmunotherapy consisting of cisplatin, DTIC, and tamoxifen combined with subcutaneous IL-2 and IFN can be safely administered in an outpatient setting. The described regimen yields moderate activity in metastatic melanoma, and efforts to improve its efficacy merit further examination.     

Flexible chemotherapy regimen with gemcitabine and vinorelbine for metastatic nonsmall cell lung carcinoma: a phase II multicenter trial

BACKGROUND: This Phase II study evaluated a flexible 3- or 4-week dosing schedule of gemcitabine and vinorelbine to determine its effect on response rate and survival of patients with metastatic nonsmall cell lung carcinoma (NSCLC). METHODS: Thirty-four response-evaluable patients, 24 with performance status (PS) 0-1 and 10 with a PS of 2, 30 with Stage IV, and 4 with Stage IIIB NSCLC were treated with gemcitabine 1000 mg/m(2) intravenously and vinorelbine 25 mg/m(2) intravenously (first 15 patients) or 30 mg/m(2) intravenously (next 19 patients) on Days 1, 8, and 15 of a 4-week cycle, if on Day 15 neutrophils were > or = 1500/uL and platelets > or = 100,000/uL. If chemotherapy could not be administered on Day 15, then Day 22 became Day 1 of the next cycle. RESULTS: When vinorelbine 25 mg/m(2) was given with gemcitabine 1000 mg/m(2), 11 patients received 4-week cycles, 3 patients 3-week cycles, and 1 patient both 3- and 4-week cycles. With vinorelbine 30 mg/m(2) and gemcitabine 1000 mg/m(2), 7 patients received 4-week cycles, 2 patients 3-week cycles, and 10 patients both 3- and 4-week cycles. The partial response rate for 34 patients was 53% (18 patients). Median survival (MS) was 11.1 months, and 1-year survival 50% (17 patients). Patients with PS 0+1 had a MS of 17.5 months compared with patients with PS 2, who had MS of 3.3 months. Patients < 70 years of age had a MS of 18 months, and those >/= 70 years had a MS of 5.5 months. CONCLUSION: This flexible schedule with gemcitabine and vinorelbine enabled optimal dose delivery and suggested excellent efficacy but less toxicity than treatment with platinum regimens.     

Front-line paclitaxel and topotecan chemotherapy in advanced or metastatic non-small-cell lung cancer: a phase II trial

Purpose: Based on previous experience, we combined topotecan with paclitaxel (weekly administration) in patients with non-small-cell lung cancer (NSCLC). Our primary objective was to determine the response rate and survival and our secondary objective, the safety of the regimen. Methods: From October 2003, until March 2005, 45 patients all with histologically or cytologically confirmed NSCLC were enrolled. All patients were chemotherapy and radiotherapy naive. Both agents were infused on day 1 of every week once for three consecutive weeks, every 28 days. Three infusions were considered as one course. The treatment plan was to give three courses (nine infusions) and then to evaluate the response. Topotecan (1.75 mg/m²) was infused for 30 min and paclitaxel (70 mg/m²) for 90 min; these doses had been established as the maximum tolerated dose in a previous phase I–II trial. Results: Eighteen/45 (40%) patients responded, 2 (4.4%) complete responses and 16 (35.6%) partial responses. Twenty-one (46.7%) patients had stable disease, and 6 (13.3%) disease progression. The median duration of response was 8 months and median time to tumor progression 9 months. Grade 3 and 4 neutropenia was observed in two patients (in these two patients, the dose of both drugs was reduced by 25% and G-CSF was given), grade 4 thrombocytopenia in one patient and grade 4 anemia in one patient. Conclusion: This novel combination of topotecan–paclitaxel in a weekly administration rendered a 40% response rate, with very low toxicity in stages IIIA, IIIB and IV NSCLC patients.     

Systemic chemotherapy for metastatic melanoma

The treatment of patients with metastatic melanoma remains a difficult problem. It is clear that more effective agents need to be developed. No single agent in conventional doses has been shown to be more effective than DTIC alone. The results obtained with detrorubicin in untreated patients are encouraging, but need further confirmation. If confirmed, combination regimens incorporating detrorubicin should be studied. Further experience is needed with high-dose cisplatin before it can be recommended for broader clinical use. Recent experience with the 4 drug combination of DTIC, BCNU, cisplatin, and tamoxifen is encouraging. The objective response rate is approximately 50% and patients with visceral disease have demonstrated regressions. CRs are not uncommon with occasional patients exhibiting durable remissions for as long as 3 years. An added benefit is that this regimen is well tolerated by most patients making it technically easy to administer. Finally, the role of interferon needs further study. The response rate to interferon alfa-2a is reasonably well defined at about 20%. Combinations of chemotherapeutic agents and interferons have only begun to be evaluated but the preliminary data are interesting.     

A phase II study of bendamustine chemotherapy as second-line treatment in metastatic uveal melanoma

Uveal melanoma is the most frequent primary malignant neoplasm of the eye and has a poor prognosis in metastatic stage. Fotemustine or a combination of gemcitabine and treosulfan has demonstrated some efficacy in metastatic disease. We conducted a phase II trial to assess the second-line activity and toxicity of bendamustine hydrochloride, a nucleoside analogue with alkylating activity. Inclusion criteria were a Karnofsky performance status of > or = 60% and progressive disease during or after first-line chemotherapy. Bendamustine was administered at a dose of 120 mg/m2 on days 1 and 2. Cycles were repeated on day 22. The primary endpoint of the study was the determination of the number of patients achieving an objective response or stable disease. The secondary endpoint was toxicity. Eleven patients were enrolled into the trial. Grade III and IV toxicity consisted of anaemia, thrombocytopenia and leucocytopenia in two, one and two patients, respectively. No grade III or IV non-haematological toxicity was observed. According to Response Evaluation Criteria in Solid Tumours (RECIST), all patients showed progressive disease. We conclude that bendamustine is ineffective as second-line chemotherapy for metastatic uveal melanoma.     

A phase 2 trial of sequential temozolomide chemotherapy followed by high-dose interleukin 2 immunotherapy for metastatic melanoma

BACKGROUND.

Previous biochemotherapy regimens for metastatic melanoma have required attenuated dosages of interleukin 2 (IL‐2) that may have compromised efficacy.

METHODS.

In a phase 2 study, the authors tested sequential temozolomide (75 mg/m² per day orally for 3 weeks) followed by high‐dose, IL‐2 (600,000 U/kg per dose intravenously; maximum, 14 doses over 5 days).

RESULTS.

Thirty‐eight patients with treatment‐naive American Joint Committee on Cancer stage IV melanoma (8 patients with M1a disease, 6 patients with M1b disease, and 24 patients with M1c disease) were enrolled. Ten patients had a history of treated brain metastases. Thirty‐one patients who received at least 2 cycles of IL‐2 were evaluable for response. Grade 3 toxicities included hyperbilirubinemia (9 patients), hematologic toxicities (leukopenia in 5 patients, thrombocytopenia in 3 patients), diarrhea (2 patients), and oliguria (1 patient). One patient had grade 4 nausea. The overall response rate (ORR) was 16% and included 3 complete responses that lasted 10.8 months, ≥32 months, and ≥36 months and 2 partial responses that lasted 13 months and 14 months. Responses were observed in patients with M1a disease and in patients with M1c disease. Sixteen patients had stable disease (15 patients progressed). The median progression‐free survival (PFS) was 5.3 months (95% confidence interval [CI], 3.7‐7.5 months). The probability of PFS at 6 months was 0.52 (95% CI, 0.33‐0.67). Among 38 enrolled patients, 16 patients remained alive at a median follow‐up of 6.7 months (range, 1.9‐36.1 months). The median overall survival (OS) was 12.1 months (95% CI, 9.1‐16.4 months), and the probability of 12‐month OS was 0.54 (95% CI, 0.34‐0.70 months).

CONCLUSIONS.

The current results indicated that it is safe to administer HD IL‐2 sequentially with temozolomide and that this combination has lower toxicity than previously used concurrent biochemotherapy regimens. However, The ORR and the durability of responses with this combination did not exceed those of single‐agent HD IL‐2. Cancer 2008. © 2008 American Cancer Society.     

Sorafenib and pegylated interferon-α2b in advanced metastatic melanoma: a multicenter phase II DeCOG trial

BackgroundThe combination of sorafenib, a multikinase inhibitor, and pegylated interferon-α2b (Peg-IFN-α2b) could potentially lead to an improved antitumoral response. Previously, combinations of interferon and sorafenib have been used in renal cell cancer.Patients and methodsPatients with stage IV metastatic melanoma and no previous systemic therapies apart from adjuvant immunotherapy received Peg-IFN-α2b 3 μg/kg once per week, and sorafenib 400-mg b.i.d. for a minimum of 8 weeks. The primary study end point was disease control rate (DCR).ResultsBetween February 2008 and February 2009, 55 patients were enrolled with a median age of 64 years (20–85). At 8 weeks, 2 patients (3.6%) had a partial response (PR) and 14 patients a stable disease (25.5%), for a DCR of 29.1% in the intention-to-treat (ITT) population. The median progression-free survival in the ITT population was 2.47 months (95% confidence interval 1.22–3.72 months). The toxicity of sorafenib and Peg-IFN-α2b combination was characterized by mainly hematological side-effects, including one treatment-related bleeding complication with a fatal outcome. Other grade 3/4 toxic effects were fatigue and flu-like symptoms.ConclusionThe combination of sorafenib and Peg-IFN-α2b showed modest clinical activity and some serious side-effects including fatal bleeding complications.     

Weekly paclitaxel and gemcitabine chemotherapy for metastatic non-small cell lung carcinoma (NSCLC): a dose-optimizing phase II trial

BACKGROUND: The current dose-optimizing Phase II study evaluated the effect of weekly paclitaxel and gemcitabine on the response rate and survival of patients with non-small cell lung carcinoma (NSCLC) using dose modifications that permitted optimal treatment intensity. METHODS: Forty-five patients (40 with TNM Stage IV and 5 with TNM Stage IIIB NSCLC) were treated with gemcitabine at 1000 mg/m(2) via a 30-minute intravenous (i.v.) infusion and with paclitaxel at 100 mg/m(2) via a 60-minute i.v. infusion. The first 3 patients received chemotherapy on Days 1, 8, and 15 every 4 weeks; the next 42 patients, participating in the Phase II trial, received chemotherapy on Days 1 and 8 every 3 weeks. RESULTS: The 3 patients who received paclitaxel and gemcitabine on Days 1, 8, and 15 every 4 weeks tolerated the treatment poorly. One patient died suddenly after Day 15 treatment during the first cycle, and the other 2 patients discontinued the treatment because of unacceptable toxicity before the third cycle of chemotherapy. The next 42 patients, 40 of whom were evaluable, entered this trial between May 2000 and April 2001. They received paclitaxel at 100 mg/m(2) i.v. followed by gemcitabine at 1000 mg/m(2) i.v. on Days 1 and 8 every 3 weeks. Two patients (5%) achieved complete response, 20 (50%) achieved partial response, and 8 (20%) had stable disease. Median survival (MS) was 9.8 months; and 1-year survival was 35%. The 32 patients with performance status (PS) 0 or 1 had an MS of 11 months; the 8 patients with PS 2 had an MS of 3 months. Toxicity (especially hematologic toxicity, neuropathy, and alopecia) was minimal. CONCLUSION: A weekly paclitaxel and gemcitabine regimen that incorporated the authors' dose modifications resulted in good efficacy with minimal toxicity.     

Treatment of metastatic breast cancer with AZQ: a phase II trial

Seventeen patients with metastatic breast cancer who had failed prior chemotherapy were treated with intravenous AZQ at a dose of 15-20 mg/m2 weekly for four consecutive weeks followed by a two-week rest period. No responses were observed. Myelosuppression was the dose-limiting toxicity. One patient experienced massive liver infarction possibly related to AZQ. Our data suggest that this agent at the schedule and dosage used is of no benefit in pretreated breast cancer patients.     

A phase II trial of recombinant interferon alpha-2b and cisplatin in metastatic melanoma

In this phase II study 37 patients with metastatic melanoma were treated with cisplatin 100 mg/m2 every three weeks and interferon alpha-2b 10 MU subcutaneously three times weekly; 125 cycles were administered. Thirty-four patients were evaluable for response and all 37 patients were assessable for toxicity. Four patients stopped treatment with cisplatin because of severe nephrotoxicity, and six patients stopped therapy because of other toxicities. Response rate was 6/34 = 18% (95%) CI (confidence interval): 7%-35%). One patient reached complete response lasting 27+ months. Five patients obtained partial responses with a median duration of response of 7 months (range 5-15+ ). Median time to progression was 2.3 months (range 1-27+). Median survival was 5 months (range 1-27+). We conclude that the combination of high-dose cisplatin 100 mg/m2 and interferon alpha-2b is associated with unacceptable toxicity. Haematological toxicity and nephrotoxicity were pronounced and the response rate was meagre and not encouraging.