Showing papers in "Journal of Clinical Oncology in 1992"
TL;DR: Tumor response should not be considered a valid surrogate end point for survival in patients with advanced colorectal cancer in future trials, according to a meta-analysis performed on nine randomized clinical trials.
Abstract: PURPOSE
A meta-analysis was performed on nine randomized clinical trials that compared fluorouracil (5-FU) with 5-FU plus intravenous (IV) leucovorin (LV) for the treatment of advanced colorectal cancer.
DESIGN
The analysis was based on the most recently updated individual patient data from all trials. The end points of interest were tumor response and overall survival.
RESULTS
Therapy with 5-FU plus LV administered either as weekly or monthly regimens showed a highly significant benefit over single-agent 5-FU in terms of tumor response rate (23% v 11%; response odds ratio (OR), 0.45; P less than 10(-7)). This increase in response did not result in a discernable improvement of overall survival (survival OR, 0.97; P = .57). The large number of patients who did not respond to treatment in both groups, and cross-overs from 5-FU alone to 5-FU plus LV are discussed as plausible explanations for the lack of a survival difference.
CONCLUSION
These results confirm the advantage of 5-FU plus leucovorin over 5-FU alone in terms of objective tumor response. They also suggest that in planning future trials, tumor response should not be considered a valid surrogate end point for survival in patients with advanced colorectal cancer.
1,198 citations
TL;DR: Although a more toxic regimen, M-VAC was found to be superior to single-agent cisplatin with respect to response rate, duration of remission, and overall survival in patients with advanced urothelial carcinoma.
Abstract: PURPOSEA prospective randomized trial was performed to determine if the addition of methotrexate, vinblastine, and doxorubicin to cisplatin (M-VAC) imparted a response rate or a survival advantage over single-agent cisplatin in patients with advanced urothelial carcinoma.PATIENTS AND METHODSFrom October 1984 through May 1989, 269 patients with advanced urothelial carcinoma were entered onto this international intergroup trial and randomized to receive intravenous (IV) cisplatin (70 mg/m2) alone or with methotrexate (30 mg/m2 on days 1, 15, 22), vinblastine (3 mg/m2 on days 2, 15, 22) plus doxorubicin (30 mg/m2 on day 2). Cycles were repeated every 28 days until tumor progression or a maximum of six cycles. There were 246 fully assessable patients of whom 126 were randomized to cisplatin alone and 120 were randomized to the M-VAC regimen.RESULTSAs expected, the M-VAC regimen was associated with a greater toxicity, especially leukopenia, mucositis, granulocytopenic fever, and drug-related mortality. Respons...
871 citations
TL;DR: It is concluded that tumors with overexpression of the c-erbB-2 oncogene are less responsive to cyclophosphamide, methotrexate, and fluorouracil (CMF)-containing adjuvant therapy regimens than those with a normal amount of gene product.
Abstract: PURPOSETo evaluate the prognostic importance of immunocytochemically determined c-erbB-2 overexpression in the primary tumors of patients with breast cancer.PATIENTS AND METHODSPrimary tumors from 1,506 breast cancer patients (760 node-negative and 746 node-positive) who were treated in the International (Ludwig) Breast Cancer Study Group Trial V were studied. Node-negative patients were allocated randomly to either a single cycle of perioperative chemotherapy (PeCT) or no adjuvant treatment, and node-positive patients received either a prolonged chemotherapy (with tamoxifen for postmenopausal patients) or a single perioperative cycle.RESULTSTumors from 16% of the node-negative patients and 19% of the node-positive patients were found to be c-erbB-2-positive. In both groups c-erbB-2 positivity correlated with negative progesterone receptors (PR), negative estrogen receptors (ER), and high tumor grade. Lobular carcinomas were all negative, and, thus support the view that such tumors represent a defined sub...
844 citations
TL;DR: This preliminary analysis of a phase II study suggests that high-dose rTNF alpha can be administered with acceptable toxicity by ILP with dopamine and hyperhydration, and combination of rT NF alpha, rIFN-gamma, and melphalan seems to achieve high efficacy with minimal toxicity, even after failure of prior therapy withMelphalan alone.
Abstract: PURPOSETo determine the toxicity and the therapeutic efficacy of the combination of the recombinant tumor necrosis factor alpha (rTNF alpha), recombinant interferon gamma (rIFN-gamma), and melphalan, we designed a protocol using isolation limb perfusion (ILP) with hyperthermia for in-transit metastases of melanoma and recurrent sarcoma. The triple combination was chosen because of the reported synergistic antitumor effect of rTNF alpha with IFN-gamma and of rTNF alpha with alkylating agents.PATIENTS AND METHODSTwenty-three patients received a total of 25 ILPs with the triple combination. There were 19 females and four males with either multiple progressive in-transit melanoma metastases of the extremities (stage IIIa or IIIab; 19 patients) or recurrent soft tissue sarcoma (five). The rTNF alpha was injected as a bolus in the arterial line, and total dose ranged between 2 and 4 mg, under hyperthermic conditions (40 degrees C to 40.5 degrees C) for 90 minutes. The rIFN-gamma was given subcutaneously (SC) on...
711 citations
TL;DR: This meta-analysis shows a small but significant improvement in survival and a major improvement in tumor control in the thorax in patients receiving thoracic radiation therapy, but this is achieved at the cost of a small increase in treatment-related mortality.
Abstract: PURPOSEOur main purpose was to determine whether the addition of thoracic radiation therapy to systemic chemotherapy improves 2-year survival, improves local (intrathoracic) tumor control, and affects treatment-related mortality in patients with limited-stage small-cell carcinoma of the lung.DESIGNEleven randomized trials addressing this issue were identified using a computerized literature search (Medline and Cancerline) and by polling senior investigators in the field. A meta-analysis was then performed and the results of the trials were analyzed in two ways, the odds ratio (OR) (Peto) method and the risk difference method (Dersimonian and Laird).RESULTSThe overall OR for benefit of thoracic radiation on 2-year survival (ie, the odds of surviving 2 years among patients allocated to radiation compared with the odds of surviving 2 years among patients allocated to control) is 1.53 (95% confidence interval [CI], 1.30 to 1.76; chi 2 = 12.76; P less than .001). The risk difference method showed that radiatio...
708 citations
TL;DR: It is concluded that combination chemotherapy resulted in improved response rates but was associated with an increased toxicity and no improvement in overall survival.
Abstract: PURPOSEThe Southwest Oncology Group (SWOG) conducted a randomized comparison of cisplatin plus fluorouracil (5-FU) and carboplatin plus 5-FU versus single-agent methotrexate (MTX) in patients with recurrent and metastatic squamous-cell carcinoma (SCC) of the head and neck. The primary objective was to compare separately the response rates of each combination regimen to standard weekly MTX.PATIENTS AND METHODSTwo hundred seventy-seven patients diagnosed with SCC of the head and neck were randomized to one of three treatments: (1) cisplatin 100 mg/m2 intravenously (IV) on day 1 and 5-FU 1,000 mg/m2 per day for a 96-hour continuous infusion repeated every 21 days; (2) carboplatin 300 mg/m2 IV on day 1 and 5-FU 1,000 mg/m2 per day for a 96-hour continuous infusion repeated every 28 days; and (3) MTX 40 mg/m2 IV given weekly.RESULTSAll three treatment regimens were well tolerated. However, both hematologic and nonhematologic toxicities were significantly greater with cisplatin plus 5-FU compared with MTX (P = ...
689 citations
TL;DR: Intensive chemotherapy can achieve DFS for a high proportion of patients with osteogenic sarcoma and histologic response to preoperative chemotherapy cannot be assessed at diagnosis, although it is a powerful predictor of DFS.
Abstract: PURPOSEAdjuvant chemotherapy improves disease-free survival (DFS) for patients with osteogenic sarcoma (OS). We reviewed our experience with OS to determine prognostic factors, the role of preoperative chemotherapy and subsequent histologic response, and the role of salvage chemotherapy after poor initial response.METHODSFrom 1975 to 1984, we saw 279 patients with previously untreated OS without metastasis. All patients received intensive chemotherapy and underwent surgical resection of primary tumor. Chemotherapy included high-dose methotrexate; Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH); and bleomycin, cyclophosphamide, and dactinomycin (BCD). Selected patients also received cisplatin.RESULTSDFS was not affected by use of preoperative chemotherapy versus immediate surgery, by use of limb-sparing surgery versus amputation, age, sex, or dose intensity of chemotherapy. DFS did correlate with serum lactate dehydrogenase (LDH), alkaline phosphatase, primary tumor site, race, and histologic re...
628 citations
TL;DR: Although the response rate to the combination of CP plus 5-FU was superior to that achieved with single agents, survival did not improve and patients with better PS and poorly differentiated tumors had superior survival.
Abstract: Purpose To determine whether combination chemotherapy is superior to single agents for recurrent/metastatic head and neck cancer, we compared the efficacy and toxicity of cisplatin (CP) and fluorouracil (5-FU), alone and in combination in a phase III trial. Patients and methods Two hundred forty-nine patients with recurrent head and neck cancer were randomized to one of three treatments: CP (100 mg/m2) and 5-FU (1 g/m2 x 4), CP, or 5-FU every 3 weeks. Results The overall response rate to the combination (32%) was superior to that of CP (17%) or 5-FU (13%) (P = .035). Response was associated with good performance status (PS) but not with primary site, site of recurrence, histology, prior irradiation, or relative dose intensity. Median time to progression was less than 2.5 months, and there was no significant difference in median survival (5.7 months) among the groups. By multivariate analysis, patients with better PS and poorly differentiated tumors had superior survival. Hematologic toxicity and alopecia were worse in the combination arm. Conclusion Although the response rate to the combination of CP plus 5-FU was superior to that achieved with single agents, survival did not improve.
572 citations
TL;DR: Therapy with HAI of FUDR improves the survival of patients with liver metastases over colorectal carcinoma, and efficient systemic chemotherapy, such as a combination of 5-FU and leucovorin, are required to prevent extrahepatic metastases.
Abstract: PURPOSEA multicentric randomized study that compared patients who received intrahepatic arterial infusion (HAI) to a group of patients who did not receive HAI (control group) was performed for unresectable hepatic metastases from primary colorectal carcinoma.PATIENTS AND METHODSOne hundred sixty-six patients were assigned randomly to HAI of floxuridine (5 fluoro-2'deoxyuridine [FUDR]) 0.3 mg/kg/d for 14 days every 4 weeks or to the control group; this latter group, depending on the investigator's choice, was either under observation or received systemic fluorouracil (5-FU). The same regimen of systemic 5-FU also was administered to the HAI group in the event of extrahepatic progression. No crossover from the control group to the HAI group was permitted. The mean duration of follow-up was 54 months (range, 31 to 72), and 163 patients were analyzed.RESULTSA significant improvement was observed in the survival rate for the 81 patients assigned to HAI group (P less than .02) with a 1-year survival rate of 64%...
540 citations
TL;DR: This risk assessment model accurately stratified the medical risk of cancer patients with fever and neutropenia using only clinical information available on the first day of their course and confirmed low-risk patients are an appropriate population in which to study less intensive treatment strategies.
Abstract: PURPOSEThe study was undertaken to validate a clinical model for predicting the medical risk of cancer patients with fever and neutropenia.PATIENTS AND METHODSA consecutive sample of 444 cancer patients with fever and neutropenia (granulocyte count less than 500/microL) at two hospitals, a specialized cancer referral center and a university-affiliated general medical hospital, was studied to identify clinical characteristics in the first 24 hours that predict subsequent serious medical complications during the hospital stay. To control for bias, major risk factors and complications were subject to blinded review.RESULTSSerious medical complications occurred in 34% of patients with risk factors identified in a prior study, including prior inpatient status (group I), outpatients with a serious independent comorbidity (group II), or uncontrolled cancer (group III), compared with 5% of the remaining patients (group IV) (P less than .000001). Two of the complications in group IV patients were transient asympto...
524 citations
TL;DR: The addition of chemotherapy to cranial RT for initial treatment ofPCNSL significantly improved disease-free survival and contributed to overall survival; all non-AIDS patients with newly diagnosed PCNSL should be considered for combined modality therapy.
Abstract: PURPOSEPrimary CNS lymphoma (PCNSL), formerly rare, is being seen with increased frequency among apparently immunocompetent patients. Conventional treatment has consisted of whole-brain radiotherapy (RT) and corticosteroids, with a median survival of 15 to 18 months and a 3% to 4% 5-year survival. Chemotherapy has been useful in the treatment of recurrent PCNSL. In 1985 we began a treatment protocol using chemotherapy and cranial irradiation for the initial therapy of non-AIDS PCNSL.PATIENTS AND METHODSThirty-one patients (group A) completed the combined modality regimen. All had placement of an Ommaya reservoir and received pre-RT systemic methotrexate, 1 g/m2, plus six doses of intra-Ommaya methotrexate at 12 mg per dose. A full course of cranial RT (4,000-cGy whole-brain RT plus a 1,440-cGy boost) was followed by two cycles of high-dose cytarabine (ara-C), with each course consisting of two doses of 3 g/m2 ara-C separated by 24 hours and infused over 3 hours. During this period, 16 additional patients ...
TL;DR: The combination regimens EP and CAV can be considered equivalently effective induction therapies in extensive SCLC, and these two regimens are, to some degree, crossresistant.
Abstract: PURPOSEThe trial was undertaken to determine (1) the relative efficacy/toxicity of two commonly used combination chemotherapy regimens in patients with extensive small-cell lung cancer (SCLC) and (2) whether the rapid alternation of these two regimens could provide superior therapeutic results compared with either regimen alone.PATIENTS AND METHODSIn this phase III trial, 437 eligible patients were stratified by performance status (PS) and sex and were randomly assigned to receive either 12 weeks of cisplatin and etoposide (EP); 18 weeks of cyclophosphamide, doxorubicin, and vincristine (CAV); or 18 weeks of alternation of these two regimens (CAV/EP).RESULTSThere were no significant differences in treatment outcome for EP, CAV, or CAV/EP in terms of response rate (61%, 51%, 59%, respectively), complete response rate (10%, 7%, 7%, respectively), or median survival (8.6 months, 8.3 months, 8.1 months, respectively), with a non-statistically significant trend toward a longer median time to progression with a...
TL;DR: The antitumor activity demonstrated for retinoids (especially RA) alone and in combination with other agents supports the need for targeted phase II trials to define the spectrum of responsive tumors and for laboratory studies to further delineate the biologic mechanisms associated with therapeutic responses.
Abstract: PURPOSERecent reports of the dramatic antitumor effect of all-trans retinoic acid (RA) in patients with acute promyelocytic leukemia (APL) have generated renewed enthusiasm for clinical studies of retinoids for oncologic therapeutic indications. Here we provide an overview of relevant aspects of retinoid physiology and molecular biology, review preclinical studies indicating antitumor activity for retinoids, and summarize the current status of clinical investigations of retinoid use for the treatment of adult and pediatric tumors.DESIGNThe published literature was reviewed with attention to areas of retinoid research that would shed insight into the oncologic uses of retinoids.RESULTSRetinoids play critical roles during normal fetal development and induce differentiation (and/or growth inhibition) in a variety of tumor-cell lines. Retinoid effects seem to result from changes in gene expression mediated via specific nuclear receptors (termed retinoic acid receptors, RAR-alpha, -beta, and -gamma), and a spe...
TL;DR: Overexpression of HER-2/neu is associated with poor clinical outcome in a subset of node-negative patients with small, ER-positive, predominantly invasive tumors and may play a role in resistance to adjuvant chemotherapy.
Abstract: PURPOSEAmplification and/or overexpression of the HER-2/neu oncogene have been shown to correlate with poor clinical outcome in patients with axillary node-positive breast cancer. In contrast, the prognostic significance of HER-2/neu in node-negative disease is controversial. This study was undertaken to evaluate further the relationship between HER-2/neu and clinical outcome in node-negative disease.PATIENTS AND METHODSOverexpression of HER-2/neu was evaluated by permanent-section immunohistochemistry in tumors from 613 patients with long-term clinical follow-up enrolled in the Intergroup Study 0011. Patients were stratified into low-risk (n = 307) and high-risk (n = 306) groups on the basis of tumor size and estrogen-receptor (ER) status. Low-risk patients were defined as having small (less than 3 cm), ER-positive tumors and were observed without additional treatment after initial surgery. High-risk patients had either ER-negative or large (greater than or equal to 3 cm), ER-positive tumors and were ran...
TL;DR: CPT-11 is an active agent against refractory or relapsed SCLC and deserves to be studied more closely as both a single agent and in combination with other drugs to treat patients with SclC.
Abstract: PURPOSETo evaluate the activity of CPT-11, which is a new derivative of camptothecin, against refractory or relapsed small-cell lung cancer (SCLC).PATIENTS AND METHODSSixteen patients with refractory or relapsed SCLC were entered onto a prospective, non-randomized, single-institution phase II trial. All 16 patients had been pretreated heavily with some form of cisplatin-based combination chemotherapy. Five patients had received previous chemotherapy with cisplatin, vincristine, doxorubicin, and etoposide (CODE) as an induction therapy. Six patients had been treated with concurrent cisplatin and etoposide plus chest x-ray. The median time off chemotherapy was 7.3 months (range, 1.9 to 15.1 months). Patients were treated with a CPT-11 starting dose of 100 mg/m2 body surface given as a 90-minute intravenous (IV) infusion every week with subsequent doses based on toxicity. Fifteen patients were assessable for toxicity, response, and survival.RESULTSSeven patients (47%; 95% confidence limits for an overall res...
TL;DR: CPT-11 is a very active agent for NSCLC with acceptable toxicities and further trials in combination with other agents for this disease are warranted.
Abstract: PURPOSECamptothecin-11 (CPT-11) is a new semisynthetic derivative of CPT, and has been shown to inhibit DNA topoisomerase I and to have a strong antitumor activity with low toxicity in murine tumors. To evaluate the effectiveness of CPT-11 in patients with non-small-cell lung cancer (NSCLC), a phase II study was conducted between April 1989 and February 1990.PATIENTS AND METHODSSeventy-three patients were entered onto the study. All patients had had no previous therapy and had measurable disease. Their median age was 67 years (range, 34 to 75 years). Fifty-four patients had a performance status (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale, and 19 had a PS of 2. CPT-11 was given at a dose of 100 mg/m2 by intravenous 90-minute infusion once a week. The dose of CPT-11 was modified based on the WBC count obtained on the day of drug administration.RESULTSOf 72 assessable patients, 23 (31.9%) showed a partial response (95% confidence interval, 20.2% to 43.6%). Of 40 patients with a stag...
TL;DR: This study confirms the safety of surveillance after orchidectomy alone in patients with stage I nonseminomatous germ cell testicular tumor and identifies a group of patients with a high risk of relapse.
Abstract: PURPOSEA prospective study of surveillance after orchidectomy alone in patients with stage I nonseminomatous germ cell testicular tumor (NSGCT) was performed to determine the relapse-free rate and to identify the histologic criteria that predict for relapse.PATIENTS AND METHODSThree hundred ninety-six patients from 16 United Kingdom and one Norwegian centers were entered onto the study between January 1, 1984 and October 1, 1987 of whom 373 were eligible for analysis. In a previous retrospective study, we defined a prognostic index based on histologic criteria that identified a group of patients with a high risk of relapse. This index was based on the presence of venous and lymphatic invasion, undifferentiated cells, and the absence of yolk sac elements in the primary tumor.RESULTSThe 2-year actuarial relapse-free rate after orchidectomy was 75% (95% confidence interval, 71% to 79%), and the rate at 5 years was 73%. Five patients died of tumor or treatment-related complications, which resulted in a 5-year...
TL;DR: Although the duration of PR is short as expected, CRs appear to be durable and CTCb is an intensification regimen with a low mortality that delivers a significantly increased dose of agents with known activity at conventional doses in breast cancer.
Abstract: PURPOSEThe study was designed to determine the duration of complete response (CR) for patients with unresectable or metastatic breast cancer treated with high-dose cyclophosphamide, thiotepa, and carboplatin (CTCb) while responding to conventional-dose therapy.METHODSEligibility criteria included histologically documented metastatic or unresectable breast cancer, at least a partial response (PR) to conventional-dose therapy, no prior pelvic radiotherapy, cumulative doxorubicin of less than 500 mg/m3, and physiologic age between 18 and 55 years. Patients with inadequate renal, hepatic, pulmonary, and/or cardiac function or tumor involvement of marrow or CNS were excluded. Cyclophosphamide 6,000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 were given by continuous infusion over 4 days. After recovery, sites of prior bulk disease were to be radiated or resected if feasible.RESULTSOf 29 registered patients, one died of toxicity (3%; hemorrhage). CRs and PRs continued a median of 16 and 5 months after ...
TL;DR: Neutropenia is the dose-limiting toxicity, and 1.5 mg/m2 is the recommended starting dose of topotecan for both minimally and heavily pretreated patients in future phase II trials, with escalation to 2.0 mg/ m2 if treatment is well tolerated.
Abstract: Results: At doses of 1.5 and 2.0 mg/m', grade 3 and 4 neutropenia occurred in most courses; however, neutropenia was brief and rarely associated with fevers or treatment delays. Neutropenia was more severe in patients with extensive prior treatment than in minimally pretreated patients, but these differences were not substantial. At 2.5 mg/m2, topotecan induced profound and prolonged neutropenia that was frequently associated with fever and treatment delays in minimally pretreated patients. Topotecan also induced mild depressions in the rTOPOTECAN (SKF 104864), a semisynthetic watersoluble analog of camptothecin, is the first topoisomerase I-targeting agent to enter clinical cancer trials since the limited clinical development of sodium camptothecin in the early 1970s. Topoisomerase I-targeting drugs stabilize a covalent DNA-topoisomerase I complex to yield enzyme-linked DNA single-strand breaks." 6 Topoisomerase I possesses several characteristics that may be relevant to its potential use as a strategic target in cancer therapy. First, its presence in relatively high levels in both proliferating and quiescent cells suggests that its function may be independent of cellular growth rate and that topoisomerase I-targeting drugs may be active in slow-growing as well as rapidly proliferating tumors. 7 '" There is also evidence indicating that the regulation of topoisomerase I is altered in neoplastic cells, which suggests a selective cytotoxic advantage for these agents in malignant tissues compared with normal tissues. For example, cells from colon tumors have been shown to contain higher intracellular levels of topoisomerase I than normal mucosal cells." 1 Topotecan demonstrated broad antitumor activity in preclinical studies. Although topotecan was twofold less active than camptothecin against L1210 cells in vitro (concentration inhibiting 50% of growth [ICs0s], 23 v 56 hematocrit level in the majority of courses; however, precipitous drops requiring transfusional therapy occurred in 14% of courses and suggested a drug-induced hemolytic effect. Unlike sodium camptothecin, hemorrhagic cystitis was not observed. Thrombocytopenia, skin rash, diarrhea, and vomiting occurred infrequently and were modest in severity. Responses were observed in non-small-cell lung carcinoma and platinum-refractory ovarian carcinoma. Drug disposition in plasma was described by a biexponential model, with renal elimination accounting for 38.7% of drug disposition. Topotecan was rapidly hydrolyzed in vivo to a less active, open-ring form. Conclusions: Neutropenia is the dose-limiting toxicity, and 1.5 mg/m' is the recommended starting dose of topotecan for both minimally and heavily pretreated patients in future phase II trials, with escalation to 2.0 mg/m 2 if treatment is well tolerated. Non-small-cell lung and platinum-refractory ovarian carcinomas should be among those evaluated in phase II trials of topotecan. J Clin Oncol 10:647-656. © 1992 by American Society of Clinical Oncology.
TL;DR: Regression analysis showed that carboplatin AUC, prior treatment, and Eastern Cooperative Oncology Group grade performance status (PS) are predictors of tumor response, thrombocytopenia, and leukopenia, respectively and Pretreatment platelet and WBC counts are additional predictors.
Abstract: PURPOSEThe study was undertaken to define the relationship between tumor response and carboplatin area under the curve (AUC) in patients with ovarian cancer; to study the relationship between carboplatin AUC and myelosuppression in the same population; to establish the true impact of carboplatin AUC, prior therapy, and pretreatment platelet and WBC counts on toxicity; and to define an optimal carboplatin exposure for treating patients with ovarian cancer.METHODSWith the equation AUC = dose/(glomerular filtration rate [GFR]+25), carboplatin AUC (course 1) was calculated for 1,028 patients (450 previously untreated) who received single-agent carboplatin (40 to 1,000 mg/m2) for advanced ovarian cancer. GFR was measured (chromium-51-edathamil [51Cr-EDTA] or creatinine clearance) in all patients.RESULTSRegression analysis showed that carboplatin AUC, prior treatment, and Eastern Cooperative Oncology Group grade performance status (PS) are predictors of tumor response, thrombocytopenia, and leukopenia. Pretreat...
TL;DR: These data with conventional-dose salvage therapy provide results for comparison with novel salvage approaches including myeloablative therapy with autologous marrow or peripheral-blood stem-cell support.
Abstract: PURPOSEThe study was undertaken to evaluate clinical prognostic factors, probability of response to therapy, duration of response, and overall survival of patients with Hodgkin's disease relapsing from a chemotherapy-induced complete remission.PATIENTS AND METHODSStudy population comprised 107 patients with Hodgkin's disease treated with combination chemotherapy at the National Cancer Institute who relapsed after achieving a complete remission.RESULTSHalf of the relapses occurred within the first year of achieving complete remission; among patients in remission 5 years or longer, only 4% relapsed. The overall survival of the relapsed patients is projected to be 17% at 20 years, calculated from the date of relapse. Primary treatment regimen, presence of B symptoms, stage, sex, liver involvement, pleural involvement, marrow involvement, and histologic subtype did not affect the survival of relapsed patients. Only age at diagnosis (older or younger than 30 years) and length of initial remission (shorter or l...
TL;DR: This trial demonstrated that IDR was more effective than DNR in remission induction in AML.
Abstract: PURPOSEA randomized clinical trial was undertaken to compare the therapeutic effectiveness of idarubicin (IDR) to daunorubicin (DNR), and both were given in combination with cytarabine (CA) in acute myelogenous leukemic (AML) patients.PATIENTS AND METHODSNewly diagnosed patients were given a daily infusion of CA (100 mg/m2) for 7 days and were assigned randomly to receive DNR (45 mg/m2) or IDR (12 mg/m2) daily for the first 3 days. Those patients who achieved a complete remission (CR) were given three consolidation courses that consisted of CA (100 mg/m2 intravenously [IV]) and thioguanine (TG; 100 mg/m2 orally) every 12 hours for 5 days and either DNR (50 mg/m2) or IDR (15 mg/m2) on the first day of each cycle. After consolidation, patients received late intensification, which consisted of the same drugs used for induction except that the CA was given for 5 days and the anthracycline for 2 days. Four courses were planned at 13-week intervals.RESULTSThe CR rates were 75 of 105 (71%) on the IDR arm and 65 ...
TL;DR: The dorsal root ganglia was the most vulnerable neural structure and the increasing histopathologic toxicity, with an index of exposure to platinum, suggests that it is retained indefinitely in an actively neurotoxic form.
Abstract: PURPOSETo identify the major sites of platinum accumulation within neural tissues after treatment with cisplatin and to determine the relationship between cumulative dosage, time, and the development of histopathological and clinical neurotoxicity.PATIENTS AND METHODSTwenty-one patients treated antemortem with cisplatin had neural tissue harvested at autopsy. Neural tissues were assayed for platinum and examined for histopathologic evidence of neurotoxicity. The relationship between histopathologic neurotoxicity and various pharmacologic parameters was analyzed.RESULTSTissue platinum levels were found to be highest in the dorsal root ganglia and lowest in tissue protected by the blood-brain barrier. For peripheral nerve, dorsal root, and dorsal root ganglia, a linear relationship was observed between platinum levels and cumulative dose. Platinum levels in neural tissue were not observed to decrease with time. Histopathologic toxicity closely matched an index of exposure to platinum (cumulative dose and lo...
TL;DR: It is concluded that knowledge of PgR levels together with other clinical information can improve the pretreatment assessment of ER-positive breast cancer patients with metastatic disease.
Abstract: PURPOSESouthwest Oncology Group (SWOG) protocol 8228 is a prospective trial designed to investigate the prognostic significance of progesterone receptor (PgR) levels in estrogen receptor (ER)-positive breast cancer patients who were treated with tamoxifen. This study was undertaken because the value of PgR measurements in advanced breast cancer had been assessed previously only in studies that were small, retrospective, or included heterogeneously treated patients.METHODSReceptor assays were performed only in the laboratories that met strict quality control guidelines. Of the 398 patients entered, 342 patients were eligible and assessable for the study end points of objective clinical response, time to treatment failure, and overall survival.RESULTSMultivariate analysis shows that elevated PgR levels significantly and independently correlated with increased probability of response to tamoxifen, longer time to treatment failure, and longer overall survival. Overall response rate (defined as complete respon...
TL;DR: M + P is superior for patients with an intrinsically good prognosis and inferior for those patients with a poor prognosis, which implies that reliable prognostic factors could be established for this disease and used to select therapy for individual patients.
Abstract: PURPOSEA meta-analysis was performed to compare survival after treatment with melphalan and prednisolone (M + P) with that after combination chemotherapy (CCT) in patients with multiple myeloma.METHODSMeta-analysis was performed on 18 published trials comprising 3,814 patients comparing M + P with CCT. Two-year survival percentages with observed and expected deaths at 2 years were calculated for each trial, and the overview methodology was applied to these figures.RESULTSOverall results from the 18 trials suggest that there is no difference in efficacy between the two treatments. This finding, however, masks a highly significant correlation between 2-year survival rates for M + P-treated patients in individual studies and the difference between the M + P and CCT 2-year survival rates for that study (r = .69; P = .0008). In separate overviews, those studies with a high M + P 2-year survival rate showed a survival difference in favor of M + P (P = .02), whereas those with a low rate suggested a difference i...
TL;DR: One can forecast final IQ score based on the initial IQ score, dose of irradiation, and age at time of irradiations, and the findings should aid in the selection of appropriate therapy when whole-brain irradiation is needed.
Abstract: PURPOSEDecline in intelligence can occur after whole-brain cranial irradiation for childhood malignancy. The purpose of this analysis was to estimate better the impact of dose and age at time of irradiation on IQ decline.PATIENTS AND METHODSA total of 48 children were studied. We combined two previously reported studies that included 15 patients with pediatric acute lymphocytic leukemia (ALL) and 18 pediatric patients with medulloblastoma/posterior fossa primitive neural ectodermal tumors (PNETs) in whom serial IQ tests were administered. Another 15 patients (nine ALL and six PNET) were studied subsequent to these reports. This experience included ALL patients who were treated with whole-brain irradiation at doses of 18 Gy (n = 9) and 24 Gy (n = 15), and PNET patients who were treated with 18 Gy (n = 5), 22 to 24 Gy (n = 2), and 32 to 40 Gy (n = 17). Multiple regression models were constructed to estimate expected IQ score after treatment based on initial IQ score, age at treatment, and dose of whole-brai...
TL;DR: Optimal cosmesis and minimal complication risk require careful attention to the technical details of surgery and radiotherapy.
Abstract: PURPOSEThe study was undertaken to assess the relationship among cosmesis and complications to factors related to disease presentation, surgical and radiotherapeutic technique, and adjuvant systemic therapy in conservative treatment for early-stage breast carcinoma.PATIENTS AND METHODSBetween 1982 and 1988, 234 women with stage I/II breast carcinoma were treated with conservation therapy by a highly standardized protocol of limited excision and radiotherapy. Radiation boost and/or reexcision were determined by careful quantitation of the normal tissue margin around the primary tumor. Boosts to 20 Gy were preferentially performed with interstitial iridium-192 (192Ir) implants. Axillary node dissections were performed in all patients aged less than 70 years. Adjuvant therapy consisted of cyclophosphamide, methotrexate, (doxorubicin), and fluorouracil (CM[A]F) six to eight times for node-positive premenopausal women and tamoxifen for node-positive or -negative postmenopausal women. Median follow-up was 50 mo...
TL;DR: Data from this study add further weight to the conclusion that breast conservation using lumpectomy and breast irradiation is equivalent to mastectomy in terms of survival and ultimate local control for stage I and II breast cancer patients.
Abstract: PURPOSEMastectomy versus excisional biopsy (lumpectomy) plus radiation for the treatment of stage I and II breast cancer was compared in a prospective randomized study.PATIENTS AND METHODSFrom 1979 to 1987, 247 women were randomized and 237 were treated on this study. All patients received a full axillary dissection and all node-positive patients received adjuvant chemotherapy with cyclophosphamide and doxorubicin. Radiation consisted of external-beam therapy to the whole breast with or without supraclavicular nodal irradiation followed by a boost to the tumor bed.RESULTSThe minimum time on the study was 18 months and the median time on the study was 68 months. No differences in overall survival or disease-free survival were observed. Actuarial estimates at 5 years showed that 85% of mastectomy-treated patients were alive compared with 89% of the lumpectomy/radiation patients (P2 = .49; 95% two-sided confidence interval [CI] about this difference, 0% to 9% favoring lumpectomy plus radiation). The probabil...
TL;DR: Findings support the validity of the simple QL measures used in the trial, which are compatible with the simple explanation that patients perceive disease progression before it is clinically evident, but also with a causal relationship between QL and survival duration.
Abstract: PURPOSEWe observed that quality-of-life (QL) scores, collected to evaluate treatment in a randomized trial in advanced breast cancer, predicted survival duration. This report explores the prognostic associations between QL and survival in more detail.PATIENTS AND METHODSIn a randomized clinical trial comparing intermittent and continuous therapy policies for patients with advanced breast cancer, QL was measured by linear analog self-assessment (LASA) and the Quality-of-Life Index (QLI). Baseline scores and subsequent changes were included in statistical models of survival duration, with and without other prognostic factors.RESULTSPhysician assessment of QLI and patient LASA scores for physical well-being (PWB), mood, nausea and vomiting, appetite, and overall QL (but not pain) at the commencement of treatment were significant predictors of subsequent survival. Scores for PWB and QLI were independent of other prognostic factors. Changes in scores were also prognostically important. Both baseline and change...