bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychosocial symptomatology, personal growth, and development among young adult patients following the diagnosis of leukemia or lymphoma.
Authors: Daiter S , Larson R A , Weddington W W , Ultmann J E
Published: February 2017

Leukemias and lymphomas, especially Hodgkin's disease, are common cancers in young adults. Young adulthood is also a critical period for psychological and social development. The occurrence of cancer can interfere with the development of independence, self-image, and life goals of young adult patients. Young adult patients with leukemia or lymphoma, especially those with less favorable prognoses, experience areas of significant personal growth and maturation during their illness and treatment. Close family and social supports report as much psychosocial stress, and in many cases more stress, than the patients themselves, but similar patterns of personal growth are rarely seen.
Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer--report of a Canadian multicenter randomized trial.
Authors: Rapp E , Pater J L , Willan A , Cormier Y , Murray N , Evans W K , Hodson D I , Clark D A , Feld R , Arnold A M
Published: February 2017

The survival benefit of combination chemotherapy to patients with advanced non-small-cell carcinoma of the lung (NSCLC) is controversial. To study this question, the National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a prospective randomized trial comparing best supportive care (BSC) to two chemotherapy regimens, vindesine and cisplatin (VP), and cyclophosphamide, doxorubicin, and cisplatin (CAP). Between February 1983 and January 1986, 23 centers across Canada entered 251 patients on study. Eighteen centers participated in the three-arm schema (150 patients); centers choosing not to participate in a study with a no-chemotherapy arm followed a two-arm schema comparing VP with CAP (101 additional patients). Altogether, 233 patients were eligible. Patients had measurable or evaluable disease, with either distant metastases (82.5%) or bulky limited disease considered inoperable or unsuitable for radical radiotherapy. The treatment groups were comparable in terms of age, sex, performance status, histology, disease extent, and weight loss. The overall response rates (complete response [CR] plus partial response [PR]) on the chemotherapy arms were CAP, 15.3%, and VP, 25.3% (P = .06). Patients on the three-arm portion of the trial had a median survival of 32.6 weeks when treated with VP, 24.7 weeks with CAP, and 17 weeks with BSC. The significance of the differences in survival, adjusted for prognostic factors, is as follows: chemotherapy v BSC, P = .02; VP v BSC, P = .01; and CAP v BSC, P = .05. Toxicity on the chemotherapy arms was significant, with leukopenia of severe or greater degree occurring in 37.8% (CAP) and 40.0% (VP), severe vomiting in 12.2% (CAP) and 23.3% (VP), and severe neurotoxicity in 15.6% (VP).
Control of chemotherapy-induced diarrhea with the synthetic enkephalin BW942C: a randomized trial with placebo in patients receiving cisplatin.
Authors: Kris M G , Gralla R J , Clark R A , Tyson L B , Groshen S
Published: February 2017

Diarrhea commonly occurs following the administration of cisplatin. BW942C, a pentapeptide, is a synthetic enkephalin shown to control castor oil-induced and traveler's diarrhea. To assess the safety and efficacy of BW942C in controlling diarrhea caused by cisplatin, 30 adults with lung cancer who had already experienced diarrhea (three or more loose bowel movements) during the 24-hour period following a prior cisplatin administration were randomized to receive either BW942C or placebo during the next cisplatin course. All patients received a concomitant antiemetic regimen including metoclopramide, dexamethasone, and lorazepam during all courses. Patients administered BW942C experienced less diarrhea (27% v 67%, P = .02). Twenty-seven percent of patients given the pentapeptide had loose bowel movements as opposed to 93% who received placebo (P = .0002). There were no significant differences in the incidence and degree of vomiting and other treatment-related side effects observed between the placebo and treatment groups. We conclude that oral BW942C is more effective than placebo in controlling diarrhea following cisplatin chemotherapy.
Chemical modifiers of cancer treatment.
Authors: Coleman C N , Bump E A , Kramer R A
Published: February 2017

Chemical modification is a concept in cancer therapy in which the state of tumor cells or normal tissues is modified such that a therapeutic gain can be achieved using conventional therapeutic modalities. Hypoxic zones targeted as cells within them may be radiation resistant, poorly perfused by chemotherapeutic agents, and possibly drug resistant due to hypoxia-related gene amplification. Nitroimidazoles have gained particular attention as chemical modifiers because they can increase the radiation sensitivity of hypoxic cells, are cytotoxic to hypoxic cells, can increase sensitivity to chemotherapeutic agents, and are useful for imaging hypoxic cells. While both radiosensitization and chemosensitization require hypoxia, the mechanism of the enhancement of each of the modalities is different. The 2-nitroimidazole hypoxic sensitizers SR 2508 and Ro-03-8799, which are less toxic than the prototype misonidazole (Miso), are in clinical trials, and dual function molecules that include a hypoxic sensitizer and alkylating function are being developed. The presence of both acutely and chronically hypoxic cells in animal tumors has been demonstrated by new imaging techniques. Oxygen delivery to tumors is being altered by the use of perfluorocarbons, and agents that alter hemoglobin affinity for oxygen. Compounds that are selectively toxic to hypoxic cells are being developed. Nonhypoxic modifiers are also being investigated. Thiol modification, particularly the alteration of glutathione concentration, has complex effects on the cell's biochemistry, in addition to affecting the competition between oxygen and thiol groups for the restoration and fixation of radiation-induced radicals. WR-2721 is being studied as a means of reducing the normal tissue toxicity of radiation and chemotherapy. Increased thiol concentration may be a mechanism of cross-resistance between certain chemotherapeutic agents and radiation.
Dose-response in the treatment of hypercalcemia of malignancy by a single infusion of the bisphosphonate AHPrBP.
Authors: Thiébaud D , Jaeger P , Jacquet A F , Burckhardt P
Published: February 2017

Fifty-two patients with malignant hypercalcemia were treated with a single dose of 3-amino-1-hydroxypropylidene-1,1- bisphosphonate (AHPrBP, previously APD), a potent inhibitor of osteoclast-mediated bone resorption. In order to establish a dose-response in humans, patients were divided into four groups receiving 30 mg, 45 mg, 60 mg, or 90 mg, respectively, as a 24-hour infusion. Initial plasma calcium was similar in all groups, except in the group receiving 90 mg, of which some patients had higher initial values. All patients responded to AHPrBP with a rapid decrease of plasma calcium concentration from 3.47 +/- 0.10 mmol/L at day 0 to 2.43 +/- 0.06 at day 6 (P less than .001). Plasma calcium became normal within four to six days in 43 patients. Eight of the nine patients whose calcium did not become normal were in the low-dose (30 and 45 mg of AHPrBP) groups. Slight and asymptomatic hypocalcemia occurred in only tow of the 26 patients in the low-dose groups, but in six of the 26 patients in the high-dose groups. A follow-up study in 40 patients showed that hypercalcemia recurred within 1 month in five of ten patients in the group receiving 30 mg, in three of ten patients in the group receiving 45 mg, and in one of 20 patients in the groups receiving 60 and 90 mg, whereas mortality was almost identical in all four groups. In all groups, plasma phosphate, plasma creatinine, urinary calcium, and hydroxyproline excretion decreased significantly. In conclusion, when administered as a single-day infusion in the treatment of tumor hypercalcemia, AHPrBP leads to a dose-dependent decrease in plasma calcium. To prevent transient hypocalcemia and early relapse, the optimal dose should be adapted to the degree of severity of hypercalcemia.
Testicular lymphoma: improved outcome with early brief chemotherapy.
Authors: Connors J M , Klimo P , Voss N , Fairey R N , Jackson S
Published: February 2017

We investigated the impact of early brief chemotherapy on the natural history of primary testicular lymphoma. We compared the outcome for patients seen before 1980--a group primarily managed with orchiectomy and regional radiation--with those seen from 1980 to 1986--a prospectively and consecutively gathered group who were offered brief chemotherapy in addition to standard orchiectomy and irradiation. The historical and study groups were similar in clinical characteristics. However, the chemotherapy group had a better relapse-free survival, 93% v 50% (P less than .02), and overall survival, 93% v 50% (P less than .02). With a median follow-up of 44 months in the chemotherapy group, it is clear that the use of early, brief chemotherapy strongly alters the natural history of testicular lymphoma by preventing relapses, the large majority of which occur early after regional therapy. We conclude that a program incorporating orchiectomy, early brief chemotherapy, and involved-field radiation therapy confers the following benefits on patients with primary testicular lymphoma: (1) laparotomy is not needed for staging; (2) relapses, including those in the opposite testicle and CNS, are largely prevented; and (3) toxicity can be kept to a modest level acceptable in elderly patients.
Pharmacology and phase I/II study of continuous intravenous infusions of iododeoxyuridine and hyperfractionated radiotherapy in patients with glioblastoma multiforme.
Authors: Kinsella T J , Collins J , Rowland J , Klecker R , Wright D , Katz D , Steinberg S M , Glastein E
Published: February 2017

Forty-seven adult patients with glioblastoma multiforme (GBM) were treated in a phase I/II study combining continuous intravenous (IV) infusions of iododeoxyuridine (IdUrd) and hyperfractionated radiation therapy. IdUrd was administered as a continuous infusion (24 h/d) for two separate 14-day infusion periods. The dose of IdUrd was escalated from 500 to 1,200 mg/m2/d. The initial wide-field tumor volume was treated to 45 Gy at 1.5 Gy fractions twice daily over 3 weeks. Following a planned 2-week break, a reduced-field boost of 25 Gy was delivered using 1.25 Gy fractions twice daily over 2 weeks (total dose, 70 Gy over 9 weeks). The IdUrd infusion preceded both the wide-field and reduced-field irradiation by 1 week. All treatment was performed on an outpatient basis. Dose-limiting systemic toxicity to the bone marrow (primarily thrombocytopenia) and gastrointestinal (GI) tract (both stomatitis and diarrhea) established the maximum tolerable dose (MTD) at 1,000 mg/m2/d for a 14-day infusion. Significant local toxicity (within the radiation field) was not seen. The kinetics of IdUrd were linear with dose escalation and reached steady-state plasma concentrations of 1.3 to 3.4 mumol/L. The total body clearance of IdUrd was .82 L/min/m2. The primary metabolite, 5-iodouracil (IUra) approached steady state by day 6 of the infusion when plasma levels were 60 times higher than IdUrd. Plasma levels of uracil and thymine, but not thymidine, were elevated throughout the infusion. With a minimum follow-up of 1 year, ten patients remain alive, while 33 patients died of progressive disease, and four patients died of other causes (including one treatment-related death). The median survival for all 47 patient and for the 40 patients receiving the MTD was 45 and 47 weeks, respectively, with 12% and 14% survivals at 24 months. Using a Cox regression analysis, age (less than or equal to 50 years v greater than 50 years) and pretreatment performance status (PS) (Eastern Cooperative Oncology Group [ECOG]-PS 0 to 1 v PS 2 to 3) were independent, statistically significant (P2 less than .05) predictors of survival, with the ECOG status being a better predictor. Patients with a PS 0 to 1 (28 patients) had a median survival of 64 weeks with 21% survival at 24 months, compared with a median survival of 29 weeks and 0% survival at 12 months in the 19 patients with PS 2 to 3. The overall and subgroup survival data are at least comparable to other combined modality treatment approaches in patients with GBM.
A randomized trial of standard chemotherapy v a high-dose chemotherapy regimen in the treatment of poor prognosis nonseminomatous germ-cell tumors.
Authors: Ozols R F , Ihde D C , Linehan W M , Jacob J , Ostchega Y , Young R C
Published: February 2017

We performed a prospective randomized trial of a high-dose chemotherapy regimen v standard cisplatin-based chemotherapy in poor prognosis nonseminomatous germ-cell cancer patients. The high-dose regimen consisting of twice the standard dose of cisplatin (P), along with vinblastine (Ve), bleomycin (B), and the epipodophylotoxin etoposide (VP-16) (V) (PVeBV) was compared to the classic regimen with normal dose cisplatin, vinblastine, and bleomycin (PVeB). Eligibility criteria included large abdominal masses, liver metastases, multiple pulmonary metastases, brain metastases, marked elevations in serum tumor markers (alpha-fetoprotein greater than 1,000 ng/mL or the beta-subunit of human chorionic gonadotropin greater than 10,000 mIU), unfavorable histology (pure choriocarcinoma), or extragonadal germ-cell tumors. Fifty-two consecutive patients with poor prognostic features were randomized to receive either PVeBV or PVeB. The median follow-up is 4 years. Treatment with the high-dose regimen increased the complete remission rate (88% v 67%, P = .14) and was associated with a lower relapse rate (17% v 41%, P = .2). The median survival of patients receiving standard therapy was 30 months, while the median survival for patients receiving the high-dose regimen has not been reached. Actuarial 5-year survival for patients treated with the high-dose regimen is 78%, compared with 48% for patients receiving standard therapy (two-sided Mantel-Cox test = .06). Disease-free survival was also superior for patients randomized to PVeBV (P = .03). Sixty-eight percent of patients (23 of 34) randomized to PVeBV are alive and continuously disease-free, compared with 33% (six of 18) for PVeB (P = .02). The major difference in toxicity between the high-dose regimen and standard therapy was the severity of myelosuppression and the incidence of severe hearing loss. Ninety-one percent of patients treated with PVeBV had a WBC count less than 1,000/microL, compared with 50% of patients receiving PVeB (P less than .05). Hearing aids were recommended for 12 patients who received PVeBV and two who received PVeB. The increased effectiveness of the PVeBV regimen in poor prognosis germ-cell cancer patients may relate to the double-dose cisplatin, the addition of VP-16, or to a synergistic effect of these two drugs.
The significance of residual mediastinal abnormality on the chest radiograph following treatment for Hodgkin's disease.
Authors: Radford J A , Cowan R A , Flanagan M , Dunn G , Crowther D , Johnson R J , Eddleston B
Published: February 2017

The chest radiographs (CXRs) of 110 patients with mediastinal Hodgkin's disease (HD) were reviewed to determine the incidence, degree, and significance of mediastinal abnormalities following treatment. Residual mediastinal abnormalities were defined as either minimal or measurable, and occurred in 64% of all patients at the completion of treatment, but were more common in those with bulky mediastinal disease at presentation (40 of 48, 83%). Fifty-one patients with a mediastinal abnormality at the end of treatment had follow-up films available. Partial or complete regression of the abnormality occurred by 1 year in 30 of these patients (59%). Over a median follow-up of 80.5 months, there were more relapses (13 of 70, 19%) in patients with residual abnormalities following treatment than in those where the mediastinum was considered normal (four of 40, 10%). Measurable abnormality was associated with a higher relapse rate (six of 25, 24%) than minimal abnormality (seven of 45, 16%), but none of these differences were statistically significant. the subsequent relapse rate for patients with persisting abnormality at 1 year was 14%, compared with 17% for patients in whom regression had occurred and 14% in whom the mediastinum had always been considered normal. Considering the whole group, the presence of a mediastinal abnormality following treatment did not predict for relapse, but for the 34 patients treated by chemotherapy (CTR) alone, a residual abnormality was associated with a significantly higher relapse rate (P = .029). We conclude that following mediastinal radiotherapy (XRT) administered either alone or combined with CTR, residual mediastinal abnormalities do not indicate the need for further treatment. However, following CTR alone, such abnormalities may signify persisting disease and we recommend that XRT be considered for these patients.
Eight drugs in one day chemotherapy in children with brain tumors: a critical toxicity appraisal.
Authors: Geyer J R , Pendergrass T W , Milstein J M , Bleyer W A
Published: February 2017

The toxicity of a new chemotherapeutic regimen for CNS tumors using eight anticancer agents administered in a 12-hour period was evaluated in 34 children with newly diagnosed and recurrent tumors treated at the Children's Hospital and Medical Center in Seattle. The chemotherapy included methylprednisolone, vincristine, lomustine (CCNU), procarbazine, hydroxyurea, cisplatin (CDDP), and either cyclophosphamide or imidazole carboximide (DTIC). The first five patients additionally received high-dose methotrexate (HDMTX), but because of excessive toxicity this was replaced by cytarabine. Of 125 courses administered without HDMTX, red cell transfusions were required in 15% of the courses and platelet transfusions were required in 8%. Hospitalization for empiric treatment of fever associated with neutropenia occurred in 6% of courses. Three episodes of documented sepsis occurred. Virtually all hematologic toxicity occurred in patients with recurrent disease. Renal toxicity occurred in 14% of patient courses. One patient died of renal failure and sepsis following therapy. Neurologic and hepatic complications were infrequent. High-frequency hearing loss above the voice range was common, but clinically significant hearing loss occurred in only three patients. Severe nausea and vomiting were infrequent. Overall, the toxicity of "eight in one" chemotherapy in newly diagnosed patients was minimal; toxicity was greater in patients with recurrent disease.
Megestrol acetate versus tamoxifen in advanced breast cancer: 5-year analysis--a phase III trial of the Piedmont Oncology Association.
Authors: Muss H B , Wells H B , Paschold E H , Black W R , Cooper M R , Capizzi R L , Christian R , Cruz J M , Jackson D V , Powell B L
Published: February 2017

One hundred thirty-eight patients with recurrent or metastatic breast cancer were randomized to receive megestrol acetate 40 mg orally four times daily or tamoxifen 10 mg orally twice a day. Upon treatment failure patients were crossed over to the alternate treatment. Eligibility required that either the estrogen receptor (ER) or progesterone receptor (PR) be positive or that both values be unknown, and that the patients be at least 2 years post-spontaneous menopause or over 50 years of age. Pretreatment characteristics including performance status (PS), disease-free interval (DFI), receptor status, and prior treatment were similar for both groups. Only three patients had previous hormonal therapy while one third had prior chemotherapy. Objective response was determined using strict International Union Against Cancer (UICC) criteria. Seventeen of 61 patients achieved complete response (CR) or partial response (PR) on megestrol (28%) while 20 of 64 patients achieved CR or PR on tamoxifen (31%). Responses of skin and bone lesions were similar for both agents; however, more patients with visceral disease responded to tamoxifen. Response did not correlate with the level of ER or PR but was correlated with age. Both unadjusted and adjusted analysis of time to progression and adjusted analysis (for pretreatment variables) of survival showed significant differences favoring tamoxifen. Six of 44 patients (14%) crossed from megestrol to tamoxifen achieved CR or PR while only two of 38 patients (5%) crossed from tamoxifen to megestrol achieved response. Only one of the original patients randomized to megestrol remains on study, while 12 patients still remain on tamoxifen. These data indicate similar response rates for megestrol and tamoxifen; however, time to progression and overall survival significantly favor tamoxifen when used as first-line therapy in this trial.
Non-Hodgkin's lymphoma of the gastrointestinal tract: an analysis of clinical and pathologic features affecting outcome.
Authors: List A F , Greer J P , Cousar J C , Stein R S , Johnson D H , Reynolds V H , Greco F A , Flexner J M , Hande K R
Published: February 2017

Clinical and histopathologic data from 87 patients with primary non-Hodgkin's lymphoma of the gastrointestinal (GI) tract diagnosed between 1974 and 1984 were reviewed. B-cell lymphomas of intermediate- or high-grade histology constituted 78% of lesions. Stage of disease varied with histologic grade, with a preponderance of advanced disease (stages IIIE and IV) in patients with low-grade lymphoma (15 of 21) (71%), compared with higher grade lesions (38%, P = .01). Among patients with nonlocalized (stages IIE through IV) lymphoma of intermediate- or high-grade histology, surgical resection of the primary focus afforded a higher rate of complete remission (CR) (70% v 50%) and sustained CR (61% v 21%, P = .04) after cytotoxic therapy compared with the nonresected cohort. The median survival in the resected group was 51 months + compared with 13 months in the nonresected patients (P = .012). Differences in outcome were attributable to a high risk of treatment-related complications (perforation and/or hemorrhage) (43% v 0%, P = .001) and local relapse (29% v 4%, P = .05) in nonresected individuals. Life-threatening local complications were not observed in patients with low-grade lymphoma managed solely with medical therapy. Histologic findings from surgically staged patients identified presence of extravisceral disease and intermediate- or high-grade tumor histology as features predictive of transmural invasion, enabling potential identification of patients who might be optimally managed by resection of the primary GI focus before initiation of cytotoxic therapy.
Early intensification of chemotherapy for childhood acute nonlymphoblastic leukemia: improved remission induction with a five-drug regimen including etoposide.
Authors: Kalwinsky D , Mirro J , Schell M , Behm F , Mason C , Dahl G V
Published: February 2017

We tested the value of early intensification of chemotherapy in 68 consecutive children with acute nonlymphocytic leukemia (ANLL) who were admitted to St. Jude Children's Research Hospital from November 1983 through March 1987. Fifty-eight patients (85%) entered complete remission after treatment with etoposide (VP-16)/cytarabine (ara-C) (A), followed by daunorubicin (Dauno)/ara-C/thioguanine (6-TG) (B) and then VP-16/azacytidine (5-AZ) (C). Thirty percent of the complete responders, mainly those with an M4 or M5 leukemia subtype, attained M1 marrow status after component A, 60% after A + B, and 10% after A + B + C. Induction failures resulted primarily from absolute or relative drug resistance; there was only one death during this phase of therapy. Postremission treatment consisted of three pairs of drugs (vincristine [VCR]/amsacrine [m-AMSA], or doxorubicin [Doxo]/6-TG/ara-C, and VP-16/cyclophosphamide [CTX]) administered sequentially in 6-week cycles for 22 months. Despite the high rate of remission induction, only 33% +/- 7% SE of the patients are expected to be failure-free survivors at 2 years. Remission durations were not significantly affected by the majority of factors examined in this study, with the exception of marrow cellularity after VP-16/ara-C induction therapy. Patients with less than or equal to 5% leukemic cells survived relapse-free for a median of 36.1 months, compared with 11.3 months for the group with a larger infiltrate (P = .01). Although postremission therapy did not improve the percentage of long-term failure-free survivors, the induction regimen we used appears highly effective, and its components should be considered for inclusion in other treatment programs.
A prospective study of cisplatin-based combination chemotherapy in advanced germ cell malignancy: role of maintenance and long-term follow-up.
Authors: Levi J A , Thomson D , Sandeman T , Tattersall M , Raghavan D , Byrne M , Gill G , Harvey V , Burns I , Snyder R
Published: February 2017

Two hundred fifty-three patients with advanced germ cell malignancy received initial chemotherapy with cisplatin, vinblastine, and bleomycin followed by surgical resection of residual masses if possible. Patients achieving complete remission (CR) were prospectively randomized to receive 6 months maintenance therapy with vinblastine or no further treatment. CR was achieved in 183 patients (72%) and a further eight patients (4%) had complete resection of residual viable malignancy (no evidence of disease [NED]). Pretreatment factors having a significant adverse influence on response by univariate analysis included extragonadal origin of the tumor, poor performance status, advanced lung or lung and abdominal disease, and elevated serum levels of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP) greater than 1,000 ng/mL. Multivariate regression analysis indicated the independent prognostic factors of significance were advanced lung or advanced lung and abdominal disease, total tumor diameter greater than 10 cm, and a serum level of HCG greater than 1,000 ng/mL. Of the toxicities encountered, myelosuppression was significant, being exacerbated by radiotherapy, and seven deaths occurred from septicemia. Bleomycin pulmonary toxicity occurred in 46% of patients and was severe in 4%, resulting in eight deaths. With a median follow-up of 64 months, relapses have occurred in 25 patients with no significant difference between those patients receiving or not receiving maintenance vinblastine. Eight of these relapses occurred beyond 1 year and four beyond 2 years of follow-up. Presently, 68% of the total patient population is alive and disease-free, with 84% of the CR and NED patients alive and 81% alive and disease-free. It is concluded that with prolonged follow-up, vinblastine maintenance therapy does not improve treatment outcome. Moreover, late relapses occur, cautioning against premature pronouncements of cure.
Pilot study of a continuous five-day intravenous infusion of etoposide concomitant with cisplatin in selected patients with advanced cancer.
Authors: Creagan E T , Richardson R L , Kovach J S
Published: February 2017

In view of experimental and clinical data suggesting enhanced antiproliferative efficacy from a continuous infusion of etoposide (VP-16) concomitant with cisplatin (CDDP), we performed a dose-seeking study of a five-day infusion of VP-16, 30 mg/m2/24 h and CDDP, 18.5 to 25 mg/m2/24 h. Among eight patients with advanced solid tumors, dose-limiting toxicities were leukopenia and thrombocytopenia. There were no clinically significant renal, neurologic, or otologic sequelae. Nausea and vomiting were mild and transient. Although the trial was not designed as a phase II assessment, we observed three objective regressions among three patients with advanced gastric adenocarcinoma who had failed prior chemotherapy. The total CDDP dose is similar to five-day single agent studies, yet the total VP-16 dose is approximately 24% to 50% less than a five-day single agent VP-16 dose. The recommended regimen for continuous 120-hour infusion is VP-16, 30 mg/m2/24 h and CDDP, 20 mg/m2/24 h, repeated at monthly intervals.
Localized neuroblastoma treated by surgery: a Pediatric Oncology Group Study.
Authors: Nitschke R , Smith E I , Shochat S , Altshuler G , Travers H , Shuster J J , Hayes F A , Patterson R , McWilliams N
Published: February 2017

A prospective study was designed to evaluate the outcome of patients with localized resectable neuroblastoma without regional lymph node involvement when no therapy beyond surgical resection was administered. One hundred one patients observed for 3 to 60 months had a 2-year disease-free survival of 89% (SE = 5%). Of the nine patients experiencing relapse, only three have died. There were no apparent distinguishing characteristics of the nine failures. Due to the favorable prognosis of the subset of neuroblastoma patients, prognostic factor analysis had very limited power and lacked clinical importance. Complete gross removal of the localized tumors is adequate therapy to ensure the survival of the majority of these patients.
Interpretation of clinical trials in diffuse large-cell lymphoma.
Authors: Armitage J O , Cheson B D
Published: February 2017

Diffuse large-cell lymphoma is one of the neoplasms curable with chemotherapy in an appreciable percentage of patients. However, all patients are not cured and the best combination of agents is not certain. This reflects the lack of completed comparative trials using the regimens that appear most effective. Despite this uncertainty, several principles for the therapy of diffuse large-cell lymphoma can be identified that allow an analysis of the results reported in the literature. These principles include the following: (1) for a regimen to be curative in a substantial number of patients it must achieve a high rate of complete remissions; (2) cure must be accomplished with frontline therapy; (3) drugs must be delivered at curative doses; (4) rapidity of achieving a complete response might be related to chance for cure; (5) prolonged treatment for diffuse large-cell lymphoma is unnecessary; and (6) aggressive therapy is toxic. In analyzing the results with any regimen it is important to have long follow-up since late relapses do occur and initial very positive results tend to decay with greater numbers of patients treated. Applying these principles to the reported chemotherapy studies in patients with diffuse large-cell lymphoma suggest that no one of the new regimens is clearly superior to the others. Also, it is not clear that cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) delivered at full doses to comparable patients is inferior to the newer regimens. The results of ongoing studies comparing these regimens might help resolve these questions.
Randomized trial of observation versus adjuvant therapy with cyclophosphamide, fluorouracil, prednisone with or without tamoxifen following mastectomy in postmenopausal women with node-positive breast cancer.
Authors: Ingle J N , Everson L K , Wieand H S , Martin J K , Votava H J , Wold L E , Krook J E , Cullinan S A , Paulsen J K , Twito D I
Published: February 2017

Following mastectomy for node-positive breast cancer, 261 postmenopausal women were randomized to observation or adjuvant treatment with cyclophosphamide, fluorouracil, prednisone (CFP) alone or combined with tamoxifen (T). Doses used were: C, 150 mg/m2 intravenously (IV) days 1 to 5; F, 300 mg/m2 IV days 1 to 5; P, 10 mg by mouth 3 times daily on days 1 to 7; and T, 10 mg by mouth 2 times daily. A total of ten courses of treatment, administered every 6 weeks, was planned and T was stopped 6 weeks after the last course of CFP. Two hundred thirty-four patients were fully eligible and evaluable. With a median observation time slightly in excess of 5 years, the proportion of recurrences on each arm were: CFP, 29 of 75 (39%); CFPT, 29 of 71 (41%); and observation, 50 of 88 (57%). Relapse-free survival distributions for both CFP and CFPT were superior to observation (both two-sided P = .01). Considering prognostic factors in covariate analysis revealed two-sided P = .0006 for CFP v observation and P = .0003 for CFPT v observation. No substantial difference was identified between CFP and CFPT. Survival data are not yet mature with 31% dead; and, although slight separations of the curves exist in favor of the treatment arms, no significant differences in survival have been seen. Both adjuvant therapy programs are well tolerated and there were no treatment-related deaths. Further maturation of the data is required to determine if the advantages in relapse-free survival will be translated into any overall survival benefit which must be considered the goal of primary interest.
Androgen priming and chemotherapy in advanced prostate cancer: evaluation of determinants of clinical outcome.
Authors: Manni A , Bartholomew M , Caplan R , Boucher A , Santen R , Lipton A , Harvey H , Simmonds M , White-Hershey D , Gordon R
Published: February 2017

We conducted a randomized clinical trial in men with stage D2 prostate cancer to test whether androgen priming potentiates the efficacy of cytotoxic chemotherapy. Eighty-five men with progressive prostate cancer refractory to orchiectomy were treated continuously with aminoglutethimide and hydrocortisone to lower adrenal androgen secretion and were administered cyclic intravenous (IV) chemotherapy. The patients were randomized to receive either androgen priming or no additional treatment for three days before and on the day of chemotherapy. Median duration of follow-up was 43 months. Response rate (remission plus disease stabilization) was not significantly different between the stimulation and control arm when the analysis was restricted to evaluable patients (79% v 73%, respectively) or when it was extended to all patients (46% v 61%). Median duration of response was similar for the stimulation and control arm (9 and 10 months, respectively). Median survival was 10 months in the stimulation and 15 months in the control group (P = .0047). The androgen sensitivity of the tumors was supported by the greater toxicity in the stimulation arm associated with androgen administration. Factors found to be independently associated with improved clinical outcome included a high Karnofsky score and hematocrit, long duration of response to the initial castration, and normalization of an elevated serum acid phosphatase on treatment. We conclude that in this group of patients with advanced disease, androgen priming does not potentiate the efficacy of chemotherapy and is actually associated with a worse outcome. Furthermore, our data emphasize the heterogeneity of biologic behavior of prostate cancer.
Evaluation of clinical competence in medical oncology training programs.
Authors: Glick J H , Chabner B A , Benson J A
Published: February 2017

The American Board of Internal Medicine (ABIM) has asked that directors of medical oncology training programs establish systems to evaluate, document, and substantiate the clinical competence of subspecialty trainees who seek certification. The Board defines the certificable medical oncologist at the completion of training as being competent to provide comprehensive and specialized medical care based on a high standard of demonstrated component skills. These skills clearly exceed those demonstrated by the certified internist. The goal of this expanded evaluation program is to ensure that the public and the profession can identify, through certification, physicians capable of providing a high standard of medical care.
A pharmacokinetic study of high-dose continuous infusion cisplatin in children with solid tumors.
Authors: Dominici C , Petrucci F , Caroli S , Alimonti A , Clerico A , Castello M A
Published: February 2017

The pharmacokinetics of cisplatin were investigated in 14 patients, aged 10 months through 13 years who were affected by solid malignant tumors. High-dose cisplatin (40 mg/m2/d) was administered with repeated courses for five days as a continuous intravenous (IV) infusion. Total platinum (Pt) levels in plasma and urine and free (protein-unbound) Pt levels in plasma ultrafiltrate were determined by inductively coupled plasma atomic emission spectrometry (ICP-AES). Areas under the concentration v time curve (AUCs) for mean total and free Pt levels were calculated for the 120-hour period of infusion and for the 384 and 120 hours following its completion, respectively. Half-lives of total and free Pt in plasma were calculated for the 216 hours following completion of infusion in five patients at their first course. The fraction of the administered Pt dose excreted in urine as Pt was determined for the five-day period of infusion and seven-day period after its completion. A total of 36 courses were studied. Maximum average Pt levels were reached after 120 hours of infusion: at the first course, 3.22 and 0.17 micrograms/mL for total and free Pt, respectively. Platinum levels declined according to a biexponential model, with initial half-lives of 18.3 and 16.9 minutes, and terminal half-lives of 81.9 and 59.0 hours as determined for total and free Pt, respectively. In the second and third courses studied there was a progressive increase in mean Pt plasma levels. Consequently, the free drug exposure as measured by AUC increased in all patients with repeated courses: 47.7% for the second and 124.4% for the third course, when compared with the first. At the same time, the mean fraction of the dose excreted in the urine for the 12-day period considered, was 44.1% for the first course, 36.2% for the second, and 28.4% for the third. The progressive enhancement of tissue exposure to the free cytotoxic drug, resulting from a reduced renal clearance of Pt with sequential courses of cisplatin, produced mainly increased toxicity while therapeutic effect progressively diminished.
Controlling delayed vomiting: double-blind, randomized trial comparing placebo, dexamethasone alone, and metoclopramide plus dexamethasone in patients receiving cisplatin.
Authors: Kris M G , Gralla R J , Tyson L B , Clark R A , Cirrincione C , Groshen S
Published: February 2017

The majority of patients receiving cisplatin at a dose of 120 mg/m2 experience delayed nausea and vomiting occurring between 24 and 120 hours after chemotherapy administration. Ninety-one patients who were receiving cisplatin (120 mg/m2) as initial chemotherapy were entered into this double-blind trial. All patients received intravenous (IV) metoclopramide, dexamethasone, and lorazepam for the control of acute emesis during the period from 0 to 24 hours after cisplatin. Patients were then randomized to one of three treatment regimens: placebo; oral dexamethasone, 8 mg twice daily for two days, then 4 mg twice daily for two days; or the combination of oral metoclopramide, 0.5 mg/kg four times daily for four days, plus oral dexamethasone administered as above. Forty-eight percent of individuals who received the two-drug combination of metoclopramide plus dexamethasone experienced delayed vomiting as opposed to 65% who were administered dexamethasone alone and 89% who received placebo (P = .006). Scores assessing the severity of delayed nausea and vomiting were consistently worse in individuals receiving placebo. The incidences of sleepiness, restlessness, heartburn, hiccoughs, loose bowel movements, insomnia, and acute dystonic reactions did not differ significantly among the three regimens and were mild and self-limited. The two-drug combination of oral metoclopramide plus dexamethasone is well tolerated, safe, and more effective than dexamethasone alone or placebo in controlling delayed vomiting following cisplatin.
Adult acute lymphoblastic leukemia: results of the Iowa HOP-L protocol.
Authors: Radford J E , Burns C P , Jones M P , Gingrich R D , Kemp J D , Edwards R W , McFadden D B , Dick F R , Wen B C
Published: February 2017

Fifty-nine consecutive previously untreated adult patients with acute lymphoblastic leukemia (ALL) were entered onto a prospective single-arm trial of doxorubicin, vincristine, prednisone, and asparaginase (HOP-L) induction therapy followed by CNS prophylaxis and 3 years of maintenance therapy. Consolidation therapy was not administered. The study population included a large number of older (greater than 50 years) patients. Seventy-five percent of patients achieved complete remission. With a median follow-up of 6 years, the median duration of complete remission is greater than 4 years, with 53% of patients expected to remain in remission at both 3 and 5 years. Overall, median survival duration is 27.9 months, with 45% and 35% of all patients expected to survive 3 and 5 years, respectively. Multivariate analysis identified patients with T-cell disease and mediastinal masses (P less than .001) and those with low values of lactic dehydrogenase (LDH) (P = .057) as being at greatest risk of relapse. Therapy was well tolerated by patients under age 35, but older patients suffered appreciable mortality. We conclude that this treatment program is effective therapy for adult ALL, yielding a large proportion of durable remissions despite the exclusion of consolidation therapy.
Similar efficacy of 6 and 18 months of therapy with four drugs (COMP) for localized non-Hodgkin's lymphoma of children: a report from the Childrens Cancer Study Group.
Authors: Meadows A T , Sposto R , Jenkin R D , Kersey J H , Chilcote R R , Siegel S E , Coccia P F , Rosenstock J , Pringle K C , Stolar C J
Published: February 2017

Successful treatment of localized non-Hodgkin's lymphoma (NHL) in childhood with 18 months of cyclophosphamide, vincristine, methotrexate (MTX), and prednisone (COMP) prompted a randomized clinical trial to determine whether a 6-month course of the same therapy was as effective as an 18-month course when combined with local irradiation. Two successive Childrens Cancer Study Group (CCSG) protocols (CCG 551 and CCG 501) entered 232 eligible patients from October 1979 until April 1986. Initially, all children with localized disease were considered eligible, but by a subsequent amendment, those with lymphoblastic (LB) histology were excluded. Hence, the study population consisted of 211 patients with nonlymphoblastic (NLB) and 21 with LB disease. Early relapses (before 6 months) occurred in 13 patients with NLB histology. Late relapses were seen in seven patients, three with LB histology. Among the 104 randomized patients who followed the prescribed therapy, there were four recurrences and no differences between 6-month and 18-month therapy. The overall survival for NLB disease was 91% on CCG 551 and 98% on CCG 501. We conclude that 6 months of COMP is excellent therapy for children with localized NLB NHL.
The use of neuroendocrine immunoperoxidase markers to predict chemotherapy response in patients with non-small-cell lung cancer.
Authors: Graziano S L , Mazid R , Newman N , Tatum A , Oler A , Mortimer J A , Gullo J J , DiFino S M , Scalzo A J
Published: February 2017

Small-cell lung cancer (SCLC), a chemotherapy-responsive disease, is characterized by neuroendocrine properties. In contrast, non-small-cell lung cancer (NSCLC) is at best moderately responsive to chemotherapy, and only 10% to 20% of cases demonstrate neuroendocrine properties. The present study is a retrospective analysis of the use of immunoperoxidase markers for neuron-specific enolase (NSE), Leu-7, and chromogranin A in NSCLC patients treated with chemotherapy. It was designed to determine if the presence of neuroendocrine markers predict for response to chemotherapy. The diagnostic slides and blocks were obtained on 52 NSCLC patients who were treated with chemotherapy (26 responders and 26 nonresponders). Immunoperoxidase studies were performed, and slides were scored without knowledge of the patient's response. Markers were positive in responders and nonresponders, respectively, as follows: NSE, 14 of 26 (54%) versus seven of 26 (27%), P = .04; Leu-7, 11 of 25 (44%) versus five of 26 (19%), P = .08; and chromogranin A, three of 26 (12%) versus 0 of 26 (0%), P = .71. Two markers were positive in 10 of 26 responders (38%) and 0 of 26 nonresponders (0%), P less than .01. Responders with two or more positive markers showed superior survival (median, 79 weeks) compared with responders with fewer than two positive markers (median, 51 weeks) and nonresponders (median, 27 weeks). These data suggest that the presence of neuroendocrine markers in NSCLC is associated with an increased likelihood of response to chemotherapy and may add to the standard parameters (performance status, weight loss) used to select patients for chemotherapy.
Biochemical modulation of fluorouracil: evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma.
Authors: Poon M A , O'Connell M J , Moertel C G , Wieand H S , Cullinan S A , Everson L K , Krook J E , Mailliard J A , Laurie J A , Tschetter L K
Published: February 2017

The purpose of this study was to evaluate the effectiveness of several new approaches designed to enhance the activity of fluorouracil (5-FU) in the management of advanced colorectal cancer. A total of 429 patients were randomized to one of the following regimens: single-agent 5-FU, given by standard 5-day, intensive-course intravenous bolus technique; 5-FU plus high-dose folinic acid (leucovorin) or 5-FU plus low-dose leucovorin; 5-FU plus high-dose methotrexate (MTX) with oral leucovorin rescue; 5-FU plus low-dose MTX; and 5-FU plus cisplatin (CDDP). The median survival for patients receiving 5-FU alone was 7.7 months. The high- and low-dose leucovorin plus 5-FU regimens had median survivals of 12.2 and 12.0 months, respectively, and offered a significant survival advantage over 5-FU alone with one-sided P values of .037 and .050, respectively (P = .051 for each treatment after correction for prognostic variables). The only other regimen possibly associated with improved survival was high-dose MTX plus 5-FU, with a median survival of 10.5 months (P = .21, P = .076 corrected). In addition, both high- and low-dose leucovorin plus 5-FU regimens were associated with significantly improved tumor response rates (P = .04 and .001) and significantly improved interval-to-tumor-progression rates (P = .015 and .007) when compared with 5-FU alone. Only the low-dose leucovorin plus 5-FU regimen was associated with significant (P less than .05) superiority in each of the following parameters of quality of life: performance status, weight gain, and symptomatic relief. The overall most therapeutically favorable regimen in this trial was 5-FU given with low-dose leucovorin; fortuitously, this regimen is associated with very low drug cost. Whereas this is the first study to demonstrate both improved palliation and survival for any regimen compared with 5-FU given by rapid intravenous (IV) injection for 5 consecutive days at a dose of 500 mg/m2/d in patients with advanced colorectal cancer, the magnitude of the gain is still relatively small. Our low-dose leucovorin plus 5-FU regimen is currently being studied in a national trial with the hope that this increased advanced disease activity may produce more substantive gains in the surgical adjuvant setting.