Phase II study of paclitaxel, ifosfamide, and carboplatin in patients with recurrent or metastatic head and neck squamous cell carcinoma

BACKGROUND: In the current study the authors assessed the antitumor activity (including response rate, duration of response, and survival) and toxicity profile (including anorexia, fatigue, emesis, and peripheral neuropathy) of a combination of paclitaxel, ifosfamide, and carboplatin (TIC) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). The trial hypothesis was that the TIC therapeutic index would be as high as that of paclitaxel, ifosfamide, and cisplatin (TIP) in this setting, but with less toxicity. METHODS: Patients with recurrent or metastatic SCCHN were treated with 175 mg/m(2) of paclitaxel as a 3-hour infusion on Day 1, 1000 mg/m(2) of ifosfamide as a 2-hour infusion on Days 1-3, 600 mg/m(2) of mesna on Days 1-3, and carboplatin (area under the concentration-time curve of 6) as a 30-minute infusion on Day 1; the regimen was repeated every 3-4 weeks. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine before paclitaxel infusion. Prophylactic hematopoietic growth factors were not given. RESULTS: Among 56 patients entered onto the study, 55 patients were analyzed for survival rates (locoregional recurrence alone in 56% of patients and distant metastasis with or without locoregional recurrence in 44% of patients). Fifty-four patients were evaluable for tumor response and toxicity. A total of 32 patients (59%) had disease that responded to treatment; the complete response rate was 17% (9 of 54 patients). The median duration of the responses was 3.7 months (95% confidence interval [95% CI], 3.4-7.8 months) and that of complete responses was 9.7 months (95% CI, 7.4 months to date of last follow-up). The median duration of follow-up care in all patients was 13.5 months. The median survival time for all patients was 9.1 months (95% CI, 7.9-12.2 months). The regimen was well tolerated. Neutropenic fever developed in 30% of the patients; 1 patient died of neutropenia and sepsis. Other toxic effects included Grade 2-3 anorexia in 13% of patients, Grade 2-3 weight loss in 11% of patients, Grade 2-3 fatigue in 27% of patients, Grade 2-3 nausea/emesis in 13% of patients, and Grade 2-3 peripheral neuropathy in 9% of patients (toxicity grading based on the National Cancer Institute's Common Toxicity Criteria). Red blood cell and platelet transfusions were required in 13% and 7% of patients, respectively. CONCLUSIONS: The TIC regimen had high antitumor activity in patients with recurrent or metastatic SCCHN, with a 59% major response rate (17% complete response rate with relatively durable complete responses). Neutropenic fever developed in 30% of the patients, the incidence of which might have been decreased by prophylactic antibiotics or hematopoietic growth factor support. Other toxic effects included significantly lower rates and less severe instances of anorexia, emesis, fatigue, and peripheral neuropathy than those reported with the previously studied TIP regimen. The TIC regimen currently is being studied as an induction chemotherapy regimen in previously untreated patients with locally advanced SCCHN. The activity of TIC (a novel paclitaxel and ifosfamide-based regimen) in patients with recurrent or metastatic SCCHN should be confirmed in a Phase III randomized trial.     

A phase II study of ifosfamide, carboplatin and cisplatin in advanced and recurrent squamous cell carcinoma of the uterine cervix

BACKGROUND:: Discouraging response durations and long-time survivals haveso far been the result of cisplatin-containing combination chemotherapyagainst advanced or recurrent squamous cell carcinoma of theuterine cervix. In order to increase the platinum-based effectupon this tumor without an increase in the specific toxicityof cisplatin, we combined it with carboplatin, added ifosfamide,which has been shown to possess a comparable degree of single-agentactivity. PATIENTS AND METHODS:: Thirty-six patients with advanced or recurrent squamous cellcarcinoma of the uterine cervix not curable by radiation orsurgery were treated with a combination of ifosfamide 1.5 gr/m²i.v. days 1–3, carboplatin 200 mg/m² i.v. day 1, and cisplatin50 mg/ml² Thirty-one patients were evaluable for response and34 patients for toxicity. RESULTS:: Twenty-three patients responded (64%), 11 (31%) of them completely,and 12 (33%) partially. Median response duration was 23 weeks(range 8–107 weeks), reaching 27 weeks and 21 weeks patientswith and without disease in previously irradiated areas, respectively.Median survival is 40 weeks (range 1–114 weeks). Toxicityconsisted mainly of moderate to severe myelosuppression, resultingin 2 toxic deaths. CONCLUSION:: The response rate, also for earlier irradiated areas, comparesfavorably with other known cisplatin-containing regimens. Thecombination deserves investigation in a randomized setting. Uterine cervical cancer, advanced, recurrent, chemotherapy     

Phase II study of liposomal doxorubicin in patients with advanced colorectal cancer

Doxil is a liposomal preparation of doxorubicin that results in prolonged pharmacologic exposure in vivo to the active agent. We sought to test the hypothesis that this new formulation would result in improved efficacy in patients with colorectal cancer. Patients with advanced colorectal cancer who had received prior therapy were eligible for the trial. Treatment consisted of Doxil 45 mg/m2 intravenously every 3 weeks. Seventeen patients entered the trial and they received a median of two cycles of treatment. None of the patients had a partial response to treatment. Stable disease was the best response, and one patient received therapy for 17 cycles before her disease progressed. The therapy was well tolerated, with only two patients having the dose decreased because of hand-foot syndrome. Four patients experienced allergic reactions during the infusion, but with appropriate premedication and slowing of the infusion, treatment was able to be resumed without difficulty. No greater than grade I neutropenia or thrombocytopenia developed in any patient. Although Doxil was well tolerated at this dose and schedule, it was not an active agent in this group of patients. Doxil alone or in combination with other agents is worthy of further study in cancers responsive to doxorubicin.     

A phase II study of liposomal doxorubicin in recurrent epithelial ovarian carcinoma

BACKGROUND: We conducted a phase II trial to evaluate the efficacy and safety of liposomal formulation of doxorubicin in recurrent ovarian carcinoma patients. METHODS: Thirty patients were included in the study after having obtained an informed consent. Their main characteristics were: median age, 64 years (range, 45-80), ECOG performance status 0 in 17 patients (56%), 1 in 11 patients (36%) and 2 in 2 patients (6.6%). Eighteen patients had metastatic disease and 12 locally advanced disease. All patients were pretreated with a platinum-based chemotherapy: 3 were considered refractory to platinum (progression or stable disease), 2 were platinum resistant (relapse < 12 months), and 7 were platinum sensitive (relapse > or = 12 months). Treatment consisted of liposomal doxorubicin, 50 mg/m2 every 4 weeks. RESULTS: The overall response rate was 26.6%, with 2 complete responses and 6 partial responses lasting 3.5 months. The incidence of grade 3-4 toxicity was 23.3% for neutropenia, 10% for mucositis and 10% for plantar-palmar erythrodysesthesia. Median survival was 12+ months (range, 2-26+). CONCLUSIONS: Liposomal doxorubicin appears to be a moderately active drug in pretreated patients, and its activity seems to be similar to that reported for other active regimens in terms of response rate. The toxicological profile of liposomal doxorubicin suggests that it may be combined with other drugs in the treatment of patients with ovarian cancer.     

Phase II trial of carboplatin plus cisplatin in recurrent and advanced squamous cell carcinoma of the head and neck

Cisplatin is one of the most active chemotherapeutic agents for the treatment of squamous carcinoma of the head and neck; however, neurotoxicity and nephrotoxicity are dose-limiting. The analog, carboplatin, is a promising new agent with similar activity but a different spectrum of toxicity. To evaluate if a therapeutic advantage could be achieved with acceptable toxicity, a combination of carboplatin 350 mg/m2 and cisplatin 50 mg/m2 were administered every 28 days to patients with recurrent or metastatic disease who had received no prior chemotherapy. Of 24 patients enrolled in this study, 21 were assessable for response and toxicity. Five partial responses were observed (24%; 95% confidence interval [Cl], 4.9% to 38.6%). No complete response occurred. Two of these patients received definitive radiotherapy and achieved complete responses. The median survival of all patients was 24 weeks. Hematologic toxicity was dose-limiting necessitating a decrease in the starting dose of carboplatin to 300 mg/m2. Nonhematologic toxicity was infrequent and mild. Significant renal impairment occurred in only two patients. Although treatment with the combination of carboplatin and cisplatin is feasible, we found no therapeutic advantage in terms of an increased response or survival.     

Phase II study of maytansine in the treatment of advanced or recurrent squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study

Twenty-nine patients with advanced or recurrent squamous cell carcinoma of the cervix who had failed standard therapy were treated with maytansine 1.2 mg/m2 intravenously once every 3 weeks. Only one partial remission was observed among the 29 patients (3%). There were no complete remissions. Stable disease was observed in 18 (62%) and progressive disease in 10 (35%). Adverse effects were infrequent and mild to moderate and consisted primarily of myelosuppression, weakness, and nausea and vomiting. This study shows that maytansine at the dose and schedule tested is essentially inactive in the treatment of advanced or recurrent squamous cell carcinoma of the cervix.     

Phase II study of pegylated liposomal doxorubicin: Inactive in recurrent small-cell lung cancer

Purpose:Although clinical experience with liposomal doxorubicinis still limited in solid tumours, single agent Caelyx (pegylated liposomaldoxorubicin) treatment has shown promising results in AIDS-related Kaposi'ssarcoma, metastatic breast and ovarian cancer and anecdotally in other solidtumours. This is the first report of its use in small-cell lung cancer (SCLC).The objective of this multicenter phase II study was to evaluate the safety,tolerance and anti-tumour activity of Caelyx as monotherapy in patients withrecurrent SCLC. Patients and methods:A total of 14 patients with recurrent SCLCwho had not received prior treatment with doxorubicin, were accrued into thisphase II study. All patients had progressed or relapsed after first-linechemotherapy. All but one had achieved objective responses to first-linetreatment with median duration of five months (range 2–18 months) buthalf of them had experienced refractory relapses (within 3–4 months).Study treatment consisted of Caelyx 50 mg/m² (1-hour i.v infusionevery 4 weeks for 6 cycles). Results:No responses were seen but in three patients disease wasstabilised for a median of three months. The median number of cycles was 2 perpatient, with 11 of 14 patients not completing 6 cycles of Caelyx treatment.From those, five patients were removed from the study after only one cycle dueto rapid disease progression, and one was withdrawn after three cycles due toprolonged toxicity. Overall, treatment was well tolerated with no episodes ofgrade 4 toxicity and only two episodes of grade 3 toxicities: one ofthrombocytopenia and one of prolonged palmar-plantar erythrodysesthesia (PPE). Conclusions:These results demonstrate limited activity of Caelyxin this patient population, which may be related to the poor prognosticfeatures of such patients. Our findings are in agreement with previousobservations that doxorubicin-containing combinations are rarely active inplatinum/etoposide failures. However, as in other studies the favourabletoxicity profile of Caelyx is confirmed.     

Pegylated liposomal doxorubicin plus carboplatin in patients with metastatic breast cancer: a phase II study

BackgroundWe determined the objective response rates produced by pegylated liposomal doxorubicin (PLD) plus carboplatin with/without trastuzumab (Herceptin).Patients and methodsPatients with measurable disease were stratified by taxane treatment history and human epidermal growth factor receptor-2 status. Treatment: PLD 30 mg/m² followed by carboplatin, day 1 of each 28-day cycle; human epidermal growth factor receptor-2 (HER2)-positive patients also received trastuzumab.ResultsArm 1 received PLD plus carboplatin (N = 41 arm 1a, taxane naive; N = 42 arm 1b, taxane pretreated); Arm 2 patients received PLD plus carboplatin + Herceptin (N = 46). Overall response rates: 31%, 31%, and 56%, respectively. Median overall survival durations were not reached in arm 1a and were 13 and 33 months for arms 1b and 2. Median progression-free survival: 8, 5, 10 months, respectively. Grades 3–4 treatment-related toxic effects for arms 1a, 1b, 2, respectively, were neutropenia 22%, 31%, 35%; thrombocytopenia 34%, 26%, 17%; and fatigue 2%, 14%, 13%.ConclusionsPLD plus carboplatin has moderate antitumor activity and excellent tolerability. Herceptin and PLD plus carboplatin in HER2-positive patients have antitumor activity without significant cardiac toxicity. Toxicity results suggest that PLD can be combined with Herceptin with minimal cardiac toxicity.     

Phase II study of pegylated liposomal doxorubicin (Caelyx) as induction chemotherapy for patients with squamous cell cancer of the head and neck

A phase II trial of pegylated liposomal doxorubicin (Caelyx) as induction chemotherapy was conducted in 20 patients with treatment-na?ve squamous cell cancer of the head and neck (SCCHN). 10 patients received two cycles of Caelyx (40 mg/m(2)) every 3 weeks before starting radical radiotherapy (RT). Subsequently, consecutive groups of 3 patients received a third escalating dose of Caelyx (10, 15 and 20 mg/m(2)) 3 days before RT. 9 of 18 (50%, 95% confidence intervals (CI): 26-74%) evaluable patients responded to Caelyx, with 11 responses in 26 (42%, 95% CI: 24-62%) evaluable sites (three complete responses (12%), eight partial responses (31%)). There was no grade 3/4 haematological, mucosal or cardiac toxicity. Nausea and vomiting were minimal. There were no drug-related RT delays. Local RT-induced toxicity was not increased. Caelyx has significant activity against SCCHN and warrants further investigation in this disease. In view of its tumour targeting properties and activity at moderate doses, it may be useful in concomitant chemoradiotherapy strategies for SCCHN.     

Phase II study of 3-AP Triapine in patients with recurrent or metastatic head and neck squamous cell carcinoma

Background: Treatment options for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) are limited with response rates to cytotoxic chemotherapy of ∼30% and median survival of 6 months.Patients and methods: In a multicentre phase II study, 32 patients with recurrent or metastatic HNSCC received 3-AP Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), an inhibitor of ribonucleotide reductase, 96 mg/m², daily for 4 days every 14 days (one cycle). Eligibility criteria required Eastern Cooperative Oncology Group performance status (ECOG PS) of zero to two with a life expectancy of >3 months; one prior chemotherapy regimen was allowed.Results: Thirty patients were assessable for response and toxicity. Median age was 57 years (range 36–79) and median ECOG PS was one (range 0–2). Thirteen patients had previously been treated with chemotherapy. A total of 130 cycles were administered with a median number of cycles of 3.5 (range 1–8). Mild anaemia (40%), nausea (22%) and fatigue (22%) were commonly reported with G3 and G4 neutropenia documented in 22% and 22%, respectively. Overall response rate was 5.9% (95% confidence interval 0.2% to 28.7%). One patient achieved a partial response, eight had stable disease and 21 progressive disease. Median time to disease progression was 3.9 months.Conclusions: 3-AP Triapine as a single agent, at this dose and schedule, is well tolerated but has only minor activity in the treatment of advanced HNSCC.     

Phase I study of carboplatin, doxorubicin and weekly paclitaxel in patients with advanced ovarian carcinoma.

BACKGROUND: Doxorubicin is an active compound in epithelial ovarian cancer (EOC), but adding it to carboplatin-paclitaxel causes toxicity. Toxicity can be reduced by weekly administration. We examined the tolerability of weekly paclitaxel in combination with carboplatin and doxorubicin. PATIENTS AND METHODS: Chemotherapy na?ve patients with EOC were treated with doxorubicin (50 mg/m(2) day 1), carboplatin (AUC 6 day 1) and paclitaxel (days 1, 8, 15, 21), 28-day cycle. Three patients were treated at each paclitaxel dose level, starting at 60, 75 and 90 mg/m(2)/week. If more than two patients in a cohort experienced dose-limiting toxicity (DLT) three more patients were treated at the dose level below. RESULTS: Twelve patients with advanced EOC received a median of six cycles (range 2-6) of the three-drug combination. DLT occurred at dose level 3: prolonged grade 4 febrile neutropenia, 1 patient; grade 3 peripheral neuropathy, 1 patient. All six patients treated at dose level 2 experienced short-lived grade 4 neutropenia, which led to dose modifications resulting in an actual delivered dose of paclitaxel of 64 mg/m(2)/week. Eight out of 12 patients had measurable disease on CT scan: four obtained a partial remission; three had stable disease. CONCLUSIONS: The combination of carboplatin, doxorubicin and paclitaxel in patients with EOC is active and its main toxicity is myelosuppression. Dose intensity of paclitaxel can be maintained in a three-drug combination through weekly administration (65 mg/m(2)).     

Methyl-CCNU, doxorubicin, and cis-diamminedichloroplatinum II in the management of recurrent and metastatic squamous carcinoma of the cervix

Twenty-three patients with recurrent unresectable carcinoma of the cervix or distant metastasis at initial presentation were treated with methyl-CCNU (175 mg/m2) and doxorubicin (45 mg/m2) on day 1 and cis- diamminedichloroplatinum II (90 mg/m2) on day 22 of a 42-day treatment cycle. Twenty-two patients had squamous carcinoma and 1 had adenosquamous carcinoma. There were two complete responses (CR), five partial responses (PR) (greater than 50% tumor reduction, greater than 3-month duration), four patients with stable disease (less than 50% reduction, greater than 3-month duration), and 12 patients who had tumor progression. One CR has been maintained greater than 28 months, and the other greater than 8 months. Total CR and PR was 7 of 23 (30.4%). Three 23 responses occurred among 15 patients (20%) who had cancer primarily confined to the pelvis, while 4 of 8 patients (50%) with distant metastasis responded. During the initial 2 cycles of chemotherapy, 12 patients had myelosuppression, defined as a leukocytes less than 3000/mm3, granulocytes less than 1,000/mm3, or platelets less than 100,000/mm3. There were no treatment-related deaths.     

Phase II study of pegylated liposomal doxorubicin in combination with gemcitabine in patients with metastatic breast cancer.

PURPOSE: We conducted a phase II clinical trial to determine the clinical efficacy and safety of pegylated liposomal doxorubicin in combination with gemcitabine in patients with metastatic breast cancer. PATIENTS AND METHODS: Patients were eligible if they had measurable disease, no prior chemotherapy for metastatic disease, and a performance status 相似文献   

Phase II study of cisplatin and vinorelbine in squamous cell carcinoma of the cervix: a gynecologic oncology group study.

PURPOSE: To evaluate the efficacy and toxicity of intravenous cisplatin and vinorelbine as combination chemotherapy in patients with advanced or recurrent squamous cell carcinoma of the cervix. PATIENTS AND METHODS: Between August 1997 and January 2001, 73 patients with advanced or recurrent squamous cell carcinoma of the cervix were entered onto this study. Eligible patients had received no prior therapeutic chemotherapy, except when administered concurrent with primary radiation therapy. The initial doses administered were cisplatin 75 mg/m(2) every 4 weeks and vinorelbine 30 mg/m(2) weekly. Subsequent doses were unchanged, reduced, escalated, or omitted according to observed toxicity and protocol guidelines. Patients were evaluated for response and toxicity using standard Gynecologic Oncology Group criteria. RESULTS: Of 73 patients, 67 were eligible and assessable. The overall response rate was 30% (five complete and 15 partial responses). The overall median response duration was 5.5+ months. The major toxicity was neutropenia, with 16% grade 3 and 67% grade 4 reported. Gastrointestinal and neurotoxicity were infrequent and mild. CONCLUSION: The combination of cisplatin and vinorelbine has moderate activity in advanced or recurrent squamous cell carcinoma of the cervix. Additional study of this regimen in a phase III setting is justified in this patient population.     

Phase II study of OSI-211 (liposomal lurtotecan) in patients with metastatic or loco-regional recurrent squamous cell carcinoma of the head and neck. An EORTC New Drug Development Group study

The purpose of this study was to evaluate the activity and safety of OSI-211, the liposomal form of lurtotecan, in patients ineligible for curative surgery or radiotherapy and with metastatic/locoregional recurrent squamous cell carcinoma of the head and neck (SCCHN) and target lesions either within a previously irradiated field (“within”) or outside a previously irradiated field (“outside”). OSI-211 was given intravenously over 30 min on days 1 and 8 at 2.4 mg/m²/day, repeated every 21 days (1 cycle). From July 2001 to March 2002, 32 patients from 14 institutions were enrolled in the “within” arm and 18 in the “outside” arm. In the “within” arm, two patients were ineligible because their tumour site was not allowed in the protocol (nasopharynx, skin) and two other patients never started treatment. Of the 46 eligible patients who started treatment, there was one objective response (response rate: 2.2% (95%Confidence Interval (CI): [0–11.5%]). Twelve patients in the “within” arm and 6 in the “outside” arm had stable disease, with a median duration of 18 weeks, 95% CI (12.7–25.7). The median time to progression was 6 weeks (95%CI: [5.9–12.7] weeks). Haematological toxicity was moderate in both arms. The most common haematological toxicity was grade 1–2 anaemia in 79% of patients. Non-haematological toxicity was mild in both arms. The most common grade 3–4 non-haematological toxicity was infection in 8.5% of patients. OSI-211 administered on d1 and d8, every 3 weeks, is well tolerated, but shows only minimal activity in locally advanced/metastatic SCCHN.     

Phase I study of pegylated liposomal doxorubicin (Caelyx) in combination with carboplatin in patients with advanced solid tumors

PURPOSE: To determine the maximum tolerated dose of the combination of Carboplatin and Caelyx, a pegylated liposomal doxorubicin, with promising activities in various solid tumors. PATIENTS AND METHODS: Twenty-two patients with various advanced solid tumors were included. Three dose levels of Caelyx were explored: 30, 35 and 40 mg/m2 in association with a fixed dose of Carboplatin (AUC 5) every 3 weeks. Dose escalation followed a modified continuous reassessment method. RESULTS: Dose-limiting toxicities were almost exclusively hematological: 3 febrile neutropenia, 1 grade 4 neutropenia lasting more than 7 days and 2 grade 4 thrombopenia were observed. Grade 4 neutropenia and febrile neutropenia were observed in 20 and 10% of courses, respectively. The median interval between courses was 25 days after cycle 1 and 27-28 days after subsequent cycles. Palmar-plantar erythrodysesthesia, mucositis and other non hematological toxicities were mild and uncommon. One patient experienced a severe anaphylactic reaction immediately after Caelyx infusion. No clinical heart dysfunction was observed. Three patients responded to therapy including 2 clinical complete responses in relapsing ovarian cancer. CONCLUSION: The recommended dose for future studies is Caelyx 35 mg/m2 + Carboplatin AUC 5 every 3 or 4 weeks. Antitumor activity, especially in ovarian cancer, warrants further investigation in phase II studies.     

Phase II study of bevacizumab with liposomal doxorubicin for patients with platinum- and taxane-resistant ovarian cancer

BackgroundSuppression of neoangiogenesis and pegylated liposomal doxorubicin (PLD) each contribute to the management of platinum-resistant/refractory ovarian cancer. The aim of this study is to test the combination of bevacizumab and PLD in women with resistant or refractory ovarian cancer.MethodsEligibility criteria were no more than two prior treatments with platinum-containing regimens and one additional regimen, without anthracyclines. Treatment was administered every 3 weeks (bevacizumab 15 mg/kg beginning on cycle 2 and PLD 30 mg/m²). The primary end point was progression-free survival (PFS) at 6 months; the secondary end points included side-effects, overall response rates (ORR) and survival (OS).ResultsForty-six patients were enrolled. The average number of courses administered was 7. The median PFS was 6.6 months (range 1–24.6 months) according to Gynecologic Cancer Intergroup Committee (GCIC) criteria and 7.8 months (range 2–13.3 months) according to Response Evaluation Criteria in Solid Tumors (RECIST). The median OS was 33.2 months (range 3–37.5+ months). The ORR was 30.2% [95% confidence interval (CI) 17.2–46.1] and the clinical benefit rate (CBR) was 86.1% (95% CI 72.1–94.7). Adverse events included mucosal and dermal erosions (30% grade 3) and asymptomatic cardiac dysfunction. Additional toxic effects included hypertension, headache, renal dysfunction and proteinuria, wound healing delay, and one episode each of central nervous system (CNS) ischemia and hemolytic uremic syndrome.ConclusionPLD with bevacizumab has improved activity in recurrent ovarian cancer with increased toxicity.     

Phase II study of single-agent panitumumab in patients with incurable cutaneous squamous cell carcinoma

BackgroundAlthough advanced cutaneous squamous cell carcinoma (CSCC) is quite common, there are few prospective trials regarding its optimal management. This study evaluated the efficacy and safety of single-agent panitumumab in the treatment of patients with CSCC not suitable for local therapy.Patients and methodsSixteen patients received single-agent panitumumab at a dose of 6 mg/kg repeated every 2 weeks for a minimum of three cycles and continued until progression, a maximum of nine cycles or dose-limiting toxicity. The primary end point was the best overall response rate (ORR) as assessed by Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) criteria. Secondary end points included evaluation of safety, toxicity and progression-free survival (PFS).ResultsBetween May 2010 and May 2012, 16 patients were recruited. Fourteen patients were male and the median age was 68 years. Fifteen patients had locoregionally advanced or recurrent disease with 14 patients receiving previous radiotherapy and 7 receiving previous cytotoxic chemotherapy. The best ORR [partial (PR) or complete response (CR)] was 31% (3/16 PR, 2/16 CR) with a further 6 of 16 patients achieving SD. The median PFS and overall survival were 8 and 11 months respectively. Grade 3 or 4 events were observed in five patients (four being skin toxicity) with one patient ceasing due to skin toxicity. With a median follow-up of 24 months, 10 patients died due to progressive disease, 6 are alive, one patient with no evidence of disease at the time of analysis.ConclusionsSingle-agent panitumumab is safe and effective in the management of patients with advanced CSCC even in a previously extensively pre-treated cohort.     

Phase II study of mitomycin-C, vincristine, and bleomycin in advanced squamous cell carcinoma of the uterine cervix.

Utilizing the stathmokinetic principle of timed vincristine and bleomycin, we combined these two agents with Mitomycin-C. The dose schedule included vincristine 0.5 mg/m2 intravenously (i.v.) geginning on day 1 and repeated twice weekly for 12 weeks; each injection was followed in 6-12 hours by bleomycin 6 mg/m2 for 12 weeks. Mitomycin-C was administered as a 20 mg/m2 bolus beginning on day 2 and repeated at 6-week intervals. Thirty patients were entered into this study, 27 were fully available for response. Thirteen patients (48%) met criteria of response (greater than 50% reduction in volume of measurable tumor). Significant myelosuppression resulted from this therapy. Median leukopenia nadir was 3.8 X 10(3) cells/mm3 and median thrombocytopenia nadir was 116 X 10(3) cells/mm3. Additional toxic reactions included anemia, lassitude, anorexia, peripheral neuropath fever, and skin rash. Despite significant, but manageable, toxicity, this combination appears to represent an improvement in the chemotherapy of a traditionaly refractory solid tumor.     

Clinical and pharmacokinetic phase II study of pegylated liposomal doxorubicin and vinorelbine in heavily pretreated recurrent ovarian carcinoma.

BACKGROUND: This multicenter phase II study evaluated feasibility, clinical efficacy, toxicity and pharmacokinetics of the combination of pegylated liposomal doxorubicin (PLD) and vinorelbine (VNR) in patients with platinum-paclitaxel pretreated recurrent ovarian cancer. PATIENTS AND METHODS: All patients received prior treatment with platinum and paclitaxel. Thirty-two heavily pretreated (median number of chemotherapy regimens two, range one to six) ovarian cancer patients received treatment with PLD 30 mg/m(2) and VNR 30 mg/m(2) every three weeks for six cycles. Ten patients entered the pharmacokinetic study, five receiving the PLD-VNR and five the VNR-PLD sequence. RESULTS: In 30 patients evaluated for response and toxicity, the overall response rate was 37% and 10% of patients achieved stable disease. Median time to progression and overall survival were 5.5 months (range 1-10) and 9 months (range 2-16), respectively. Toxicity was generally mild and reversible. VNR AUC(tot) and plasma levels were considerably higher in the PLD-VNR sequence. CONCLUSIONS: The PLD-VNR regimen exhibits significant activity in heavily pretreated patients, is well tolerated and is associated with encouraging survival. Preliminary pharmacokinetic results suggest the PLD-VNR sequence for further clinical applications. This regimen should be considered as a treatment option in patients with chemotherapy-resistant ovarian cancer.