Improvements in Survival and Clinical Benefit With Gemcitabine as First-Line Therapy for Patients With Advanced Pancreas Cancer: A Randomized Trial.

PURPOSE: Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms. To date, no treatment has had a significant impact on the disease. In early studies with gemcitabine, patients with pancreas cancer experienced an improvement in disease-related symptoms. Based on those findings, a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer. PATIENTS AND METHODS: One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were randomized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest, then weekly x 3 every 4 weeks thereafter (63 patients), or to fluorouracil (5-FU) 600 mg/m2 once weekly (63 patients). The primary efficacy measure was clinical benefit response, which was a composite of measurements of pain (analgesic consumption and pain intensity), Karnofsky performance status, and weight. Clinical benefit required a sustained (> or = 4 weeks) improvement in at least one parameter without worsening in any others. Other measures of efficacy included response rate, time to progressive disease, and survival. RESULTS: Clinical benefit response was experienced by 23.8% of gemcitabine-treated patients compared with 4.8% of 5-FU-treated patients (P = .0022). The median survival durations were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients, respectively (P = .0025). The survival rate at 12 months was 18% for gemcitabine patients and 2% for 5-FU patients. Treatment was well tolerated. CONCLUSION: This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced, symptomatic pancreas cancer. Gemcitabine also confers a modest survival advantage over treatment with 5-FU.

A phase II multicentre study of ziv-aflibercept in combination with cisplatin and pemetrexed in patients with previously untreated advanced/metastatic non-squamous non-small cell lung cancer.

BACKGROUND: This study evaluated the efficacy and safety of ziv-aflibercept in combination with cisplatin and pemetrexed in non-small cell lung cancer (NSCLC). METHODS: This single arm, multicentre phase II trial enrolled patients with previously untreated, locally advanced or metastatic non-squamous NSCLC. Patients received intravenous ziv-aflibercept 6 mg kg(-1), pemetrexed 500 mg m(-2), and cisplatin 75 mg m(-2), every 21 days for up to six cycles. Maintenance administration of ziv-aflibercept was to continue until disease progression, intolerable toxicity or other cause for withdrawal. The co-primary end points were objective response rate (ORR) and progression-free survival (PFS). Planned sample size was 72 patients. RESULTS: The study was closed prematurely because of three confirmed and two suspected cases of reversible posterior leukoencephalopathy syndrome (RPLS). A total of 42 patients were enrolled. Median age was 61.5 years; 55% were male, 86% Caucasian and 50% had Eastern Cooperative Oncology Group performance status (ECOG PS)=0. A median of four cycles of ziv-aflibercept was administered. The most common treatment-emergent adverse events (TEAEs) of any grade were nausea (69%) and fatigue (67%), with hypertension (36%) as the most common grade 3/4 TEAE. Of the 38 evaluable patients, ORR was 26% and median PFS was 5 months. CONCLUSION: Cases of RPLS had been observed in other studies in the ziv-aflibercept clinical development programme but the rate observed in this study was higher than previously observed. This might be related to declining renal function and/or hypertension. Although ORR and PFS were in accordance with most historical first-line NSCLC studies, this combination of ziv-aflibercept/cisplatin/pemetrexed will not be further explored in NSCLC.

Predictors of cervical cancer screening in Mexican American women of reproductive age.

Several barriers impede cancer prevention in the Mexican American population. This study identified sociocultural factors that could be used to increase screening rates for cervical cancer in women of reproductive age. A survey was conducted in 1991 of 366 Mexican American women ages 18 to 40 in Tucson, Arizona, to assess current compliance with cervical cancer screening guidelines and several psychological, social, and cultural variables. Women who had never been screened (13 percent of the sample) had a knowledge deficit, no gynecological care, and no sexual activity. Women not screened annually (16 percent) lacked preventive care, imperfectly understood the Pap test, had lower self-efficacy expectations for understanding physicians, experienced higher emotional stress about the test, and were older and less acculturated. Women who have never been screened require basic education on cancer and cancer screening and policy changes increasing access to care. For women with less routine screening, preventive care, supportive attitudes, and health care skills must be encouraged.

Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial.

PURPOSE: Most patients with advanced pancreas cancer experience pain and must limit their daily activities because of tumor-related symptoms. To date, no treatment has had a significant impact on the disease. In early studies with gemcitabine, patients with pancreas cancer experienced an improvement in disease-related symptoms. Based on those findings, a definitive trial was performed to assess the effectiveness of gemcitabine in patients with newly diagnosed advanced pancreas cancer. PATIENTS AND METHODS: One hundred twenty-six patients with advanced symptomatic pancreas cancer completed a lead-in period to characterize and stabilize pain and were randomized to receive either gemcitabine 1,000 mg/m2 weekly x 7 followed by 1 week of rest, then weekly x 3 every 4 weeks thereafter (63 patients), or to fluorouracil (5-FU) 600 mg/m2 once weekly (63 patients). The primary efficacy measure was clinical benefit response, which was a composite of measurements of pain (analgesic consumption and pain intensity), Karnofsky performance status, and weight. Clinical benefit required a sustained (> or = 4 weeks) improvement in at least one parameter without worsening in any others. Other measures of efficacy included response rate, time to progressive disease, and survival. RESULTS: Clinical benefit response was experienced by 23.8% of gemcitabine-treated patients compared with 4.8% of 5-FU-treated patients (P = .0022). The median survival durations were 5.65 and 4.41 months for gemcitabine-treated and 5-FU-treated patients, respectively (P = .0025). The survival rate at 12 months was 18% for gemcitabine patients and 2% for 5-FU patients. Treatment was well tolerated. CONCLUSION: This study demonstrates that gemcitabine is more effective than 5-FU in alleviation of some disease-related symptoms in patients with advanced, symptomatic pancreas cancer. Gemcitabine also confers a modest survival advantage over treatment with 5-FU.

Randomized, double blind, dose-response trial across four oral doses of dolasetron for the prevention of acute emesis after moderately emetogenic chemotherapy. Oral Dolasetron Dose-Response Study Group.

BACKGROUND: This double blind parallel group study assessed the acute antiemetic efficacy of four oral doses of dolasetron mesylate in cancer patients receiving their first course of intravenous chemotherapy with doxorubicin and/or cyclophosphamide. METHODS: Patients were randomized to receive 25, 50, 100, or 200 mg of dolasetron mesylate 30 minutes prior to chemotherapy and were monitored for nausea and emetic episodes for the next 24 hours. RESULTS: Three hundred and nineteen cancer patients at 32 sites completed the study. Most patients were female (81%); of this group, 69% had breast carcinoma. A highly statistically significant linear trend demonstrating improved response with higher doses was detected for complete response (no emetic episodes and no rescue medication) (P < 0.001), for complete plus major response (0-2 emetic episodes and no rescue medication) (P < 0.001), and for patient visual analog scale assessments of nausea (P = 0.001) and general satisfaction with antiemetic therapy (P = 0.001). No serious adverse events were noted. The most frequent adverse event was mild, self-limiting headache, which has been reported with other drugs in this class. CONCLUSIONS: Single oral doses of dolasetron mesylate were found to be effective in preventing acute emesis in cancer patients receiving moderately emetogenic chemotherapy.

Antiemetic efficacy of two different single intravenous doses of dolasetron in patients receiving high-dose cisplatin-containing chemotherapy.

This randomized, double-blind, parallel-group, multicenter study compared the antiemetic effectiveness, safety, and tolerability of two different intravenous (i.v.) doses of dolasetron mesylate (0.6 and 1.8 mg/kg) in cancer patients receiving their first course of high-dose cisplatin-containing chemotherapy (> or = 75 mg/m2). Efficacy was assessed by recording the timing, number, and severity of emetic episodes in the 24 h following high-dose cisplatin. Safety was evaluated by monitoring adverse events, vital signs, clinical laboratory parameters, and electrocardiograms. Of the 62 patients enrolled in the study, 29 received 0.6 mg/kg of dolasetron mesylate and 33 received 1.8 mg/kg. Patients who received dolasetron mesylate 1.8 mg/kg consistently experienced a greater degree of antiemetic control than those who received 0.6 mg/kg. Complete responses were achieved by 55% of patients who received 1.8 mg/kg compared with 31% for the 0.6-mg/kg group. The 1.8-mg/kg group achieved a significantly (p = 0.039) higher complete/ major response rate than the 0.6-mg/kg group (77% vs 55%, respectively) and a significantly (p = 0.004) longer time to the first emetic episode (> 24 h vs 13.5 h, respectively). More than 80% of patients were either satisfied or very satisfied with dolasetron treatment. The most common adverse events were mild to moderate in intensity, consistent with other studies, and included headache (24.1% of patients) and diarrhea (4.8%). These results demonstrated that a single 1.8-mg/kg i.v. dose of dolasetron mesylate provided effective antiemetic activity in a majority of patients given high-dose cisplatin for the first time and should be evaluated further in clinical trials.

Evaluation of race as a prognostic factor in multiple myeloma. An ancillary of Southwest Oncology Group Study 8229.

PURPOSE: The objective of this investigation was to assess the impact of race (black v white) on the survival of patients with multiple myeloma treated within the context of a large clinical trial. PATIENTS AND METHODS: A cohort of patients randomized to receive one of two treatment regimens and monitored for at least 10 years was studied to assess the impact of race as a prognostic factor, after adjusting for other known factors such as stage of disease. Patients were recruited from the referral network of the Southwest Oncology Group (SWOG), a national multiinstitutional consortium that includes both academic and community treatment centers. Patients had a diagnosis of multiple myeloma and had not previously been treated for this disease. They were carefully characterized as to demographic and clinical features, and were randomized to receive one of two treatment regimens, which proved to have virtually identical outcomes. The outcome measure was survival, measured from the date of randomization to the date of last contact. Patients still alive at last contact date were treated as censored observation. RESULTS: Survival for black myeloma patients was similar to that for white patients, both overall and adjusted for prognostic factors such as stage. CONCLUSION: Observed differences in mortality between blacks and whites cannot be attributed to differences in survival after diagnosis, given comparable treatment.

Cancer in Hispanics: issues of concern.

Hispanics are among the fastest growing minorities in the United States, after Asian-Americans and Pacific-Islanders. Hispanics, Latinos, Chicanos, Mexican-Americans, Puerto Ricans, Cuban-Americans, etc. are all designations used to describe this large, heterogeneous population with different cultural, ethnic, geographic, and social backgrounds. There is still no clear definition of the term "Hispanic." The data available regarding the incidence, morbidity, and mortality from cancer in Hispanics are scarce, scattered, outdated, and often incomplete. From the studies looking at the accessibility and availability of medical care for this population, few have examined in detail the variability within the entire Hispanic population. The aggregation of culturally distinct subgroups, which have resided in the United States for different periods of time, into a more inclusive Hispanic category assumes that all persons of Mexican, Cuban, and Puerto Rican extraction have similar needs and experience similar barriers in using health services. There is, however, no clear evidence for this assumption. On the contrary, there is evidence that each group has specific characteristics that make it different and independent from another, despite the fact that they also share some commonalities. Because of the lower overall prevalence of cancer in this population, potential protective factors need to be explored. Hispanics, however, appear to have a less favorable stage of disease at presentation and have overall lower death rates from cancer than non-Hispanic whites, but lower overall survival in certain cancers. Demographic and epidemiologic data collection need to be updated and improved.(ABSTRACT TRUNCATED AT 250 WORDS)

CT findings after hepatic chemoembolization.

Hepatic arterial chemoembolization (CE) with a mixture of particulate collagen and chemotherapeutic agents was evaluated as therapy for hepatic metastases from colorectal carcinoma. This article describes the characteristics sequential pattern of change seen on liver CT scans following CE. Thirty CT scans were performed on seven patients who had undergone a total of 11 CE procedures. All patients had baseline, immediate postprocedural, and follow-up CT exams at 1 to 2 month intervals following CE. Immediate post-procedural CT scans mapped the area of embolization owing to the density of the contrast mixed with the CE agents. Some lesions seen easily on baseline were more difficult to see as they became isodense with normal liver. Reflux of embolic material into the cystic artery and gallbladder wall was also observed on postprocedural scans in three patients. In all patients, early follow-up scans (1 month after CE) demonstrated changes in lesions seen on baseline scans consistent with tumor necrosis. This was corroborated by a decrease in carcinoembryonic antigen (CEA) levels. In three patients, however, low attenuation regions developed in areas in which there had been no lesion before. The significance of these is uncertain, but the low CEA values and the subsequent evolution in appearance of these sites on CT suggest that they were regions of hepatic ischemia/infarction as opposed to heretofore unidentifiable metastases, now "unmasked." Intermediate follow-up scans (2-3 months) revealed maximal effect on tumor volume, with a decrease of > or = 25% in five of seven patients (71%). Late follow-up scans (> or = 3 months after the last CE) confirmed recurrent disease and new lesions in all cases.

A phase I trial of fluorouracil, leucovorin, and recombinant interferon alpha-2b in patients with advanced malignancy.

We conducted a phase I trial of fluorouracil (5-FU), leucovorin, (LCV), and recombinant interferon-alpha-2b (rIFN-alpha-2b). The doses of each of the three agents were escalated sequentially. 5-FU and LCV were administered by IV bolus, weekly for 6 weeks and rIFN-alpha-2b was administered by subcutaneous injection, three times weekly for 6 weeks. Twenty-nine patients with advanced cancer (75% colon or pancreatic cancer) were treated. Partial remissions were observed in three patients (10%) with previously untreated colon cancer, colon cancer refractory to 5-FU plus LCV and previously untreated pancreatic cancer, respectively. An additional three patients with pancreatic, prostate, and rectal cancer had a 50% reduction in tumor markers but no change in objective tumor measurements. The toxicity of this regimen was tolerable. The most common toxicities were diarrhea, fatigue, flu-like symptoms, nausea/vomiting, and mucositis. However, no fatal or life-threatening toxicities were observed. We conclude that the combination of 5-FU, LCV, and rIFN-alpha-2b can be safely administered and recommend further evaluation of this regimen in patients with tumors of gastrointestinal origin using doses of 5-FU 600 mg/m2, LCV 500 mg/m2, and rIFN-alpha-2b 10 x 10(6) U.

Phase II study of fenretinide (N-[4-hydroxyphenyl]retinamide) in advanced breast cancer and melanoma.

Retinoids, the natural and synthetic analogs of vitamin A, are growth-inhibiting and differentiation-inducing agents and show clinical promise as chemopreventive and antineoplastic agents. Fenretinide, a new synthetic retinoid, has antitumor activity in certain in vitro and in vivo model systems and was relatively nontoxic in phase I trials. Based on these data, we designed a phase II study of Fenretinide involving 31 patients with advanced breast cancer [15] and melanoma [16], two cancers shown to be responsive to this agent in preclinical models. Fenretinide was inactive in patients with advanced disease. Toxicity was mild, and reversible. Mucocutaneous side effects occurred in 16 (52%) patients. Nyctalopia developed in three patients one of whom developed decreased B-wave amplitude of the scotopic electroretinogram. The minimal toxicity and significant activity in preclinical studies make this an attractive agent for future breast cancer chemoprevention studies.