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Biomedical subjects

F A Greco

Publications and source records attributed to F A Greco.

At least 91 records · Page 5Linked to original sources
PubMed1995

One-hour paclitaxel infusion schedules: a phase I/II comparative trial.

The safety and feasibility of two 1-hour outpatient paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) infusion schedules were evaluated in a randomized phase I/II study of 56 patients with a variety of resistant and refractory advanced cancers. Paclitaxel 135 mg/m2 was infused as a single dose over 1 hour or was divided into three doses infused over 1 hour on 3 consecutive days. Standard paclitaxel premedications were given. The two schedules produced similar toxicity. Total alopecia was universal. Myelosuppression was the most common severe toxicity: 19% and 2%, respectively, of the 162 courses were associated with grades 3 and 4 leukopenia. Neutropenic fever necessitated nine hospitalizations (eight patients.) Preliminary findings show objective responses in 11 patients (20%). Responders had breast, ovarian, and lung cancers. We conclude that both 1-hour paclitaxel outpatient infusion schedules are safe, and we are currently investigating a 200 mg/m2 dose and the incorporation of the 135 mg/m2 schedules into phase II combination chemotherapy regimens.

Blood Cell Count↗
PubMed1995

Paclitaxel by 1-hour infusion in combination chemotherapy of stage III non-small cell lung cancer.

We report our preliminary phase II experience with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a I-hour infusion with cisplatin, etoposide, and concurrent radiotherapy to patients with unresectable stage IIIA or IIIB non-small cell lung cancer. Twenty-three patients have been started on therapy, with 15 thus far completing treatment. Eight of 15 patients have achieved complete or "near complete" responses, and five more patients have had partial responses. No patients experienced disease progression. The combined-modality regimen was well tolerated, with the exception of grade 3 or 4 esophagitis, which usually occurred during the last 2 weeks of radiation therapy (eight patients). It is hoped the results of these and other studies will help clarify the role of paclitaxel in multimodality therapy for lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Paclitaxel in lung cancer: 1-hour infusions given alone or in combination chemotherapy.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a 1-hour infusion potentially offers its recipients reduced toxicity, demonstrated efficacy, and greater ease of administration. To confirm this hypothesis, we undertook a phase I/II study of 1-hour, single-agent paclitaxel in 164 patients' refractory malignancies; 59 patients with recurrent or stage IV non-small cell lung cancer (NSCLC) participated in the study. Our objective was to compare two paclitaxel doses (135 and 200 mg/m2) and two 1-hour infusion schedules (1 hour in 1 day, or 1 hour each day for 3 days, divided dose). Results from this study show that paclitaxel given over 1 hour possesses marked antitumor activity. In patients with NSCLC, the overall response rate was 25%, with a higher response rate among higher-dose recipients (31% v 12%). These promising results with single-agent paclitaxel prompted phase II trials of combination therapy incorporating the 1-hour paclitaxel infusion. Twenty-three patients with locally advanced, unresectable stage IIIA or IIIB NSCLC have been treated with 1-hour paclitaxel and cisplatin/etoposide plus radiation therapy. Three patients have had complete responses (CRs) and another five have had "near CRs," defined as only nonspecific abnormalities in previously irradiated areas on computed tomography. Five patients had partial responses. Although the median follow-up is only 9 months, it is encouraging that disease has recurred in only one of the eight patients with CR or near CR and that toxicity has been manageable. Another phase II trial is evaluating 1-hour paclitaxel, carboplatin, and extended-schedule etoposide in patients with limited or extensive small cell lung cancer. Of the 22 patients now evaluable for response (median follow-up, 8 months), 10 (six with limited and four with extensive small cell lung cancer) have achieved CRs and 11 have achieved partial remissions. The regimen is well tolerated. The final results of these and other phase II trials should help clarify optimal paclitaxel schedules and regimens for large-scale randomized trials in patients with lung cancer.

Adult↗
PubMed1994

Paclitaxel administered by 1-hour infusion. Preliminary results of a phase I/II trial comparing two schedules.

BACKGROUND: Paclitaxel currently is administered by prolonged intravenous infusion because of the occurrence of severe hypersensitivity reactions in patients in early clinical trials. However, intensive premedication probably is more important in eliminating allergic reactions than is the length of infusion. The authors evaluated the feasibility of two paclitaxel schedules using a 1-hour, outpatient infusion. METHODS: Fifty-six patients with advanced, refractory malignancies were randomized to receive one of two paclitaxel schedules: 135 mg/m2 administered as a single dose over 1 hour, or 135 mg/m2 administered in divided daily doses for 3 days, each over 1 hour. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. RESULTS: No serious hypersensitivity reactions occurred with either schedule of paclitaxel. In addition, other adverse effects were usually mild and easily tolerated. Other than alopecia, which occurred in all patients, myelosuppression was the most common severe toxicity. However, grade 3 leukopenia occurred in only 19% of treatment courses, and grade 4 leukopenia (nadir < 1000/microL) occurred in only 2%. Nine patients required hospitalization for treatment of infection associated with neutropenia. No significant differences in toxicity were observed when the two paclitaxel regimens were compared. Although it is too early to assess the results adequately, preliminary findings showed that thus far 11 of 56 patients (20%) had a partial or complete response to therapy. Responses were observed in patients with breast, ovarian, and lung cancer. CONCLUSIONS: Paclitaxel can be safely administered in a 1-hour infusion in an outpatient setting, either as a single dose or in divided doses for three days. Severe hypersensitivity reactions did not occur in 162 treatment courses, and neutropenia was mild in most patients. Incorporation of this dose and these schedules of paclitaxel into combination chemotherapy regimens should be feasible. An investigation of higher paclitaxel doses given in a 1-hour infusion is currently in progress.

Adult↗
PubMed1994

Prolonged administration of low dose infusional etoposide in patients with advanced malignancies. A phase I/II study.

BACKGROUND: Etoposide displays remarkable schedule dependency. To better define the optimal dose and schedule, the authors administered etoposide as a prolonged low daily dose infusion in patients with a variety of advanced malignancies. METHODS: Between October 1989 and April 1992, 40 patients met inclusion criteria and were enrolled in this study; the initial dose of infusional etoposide was 25 mg/m2/day. Doses were not escalated further, because it became evident that 25 mg/m2/day was the maximum tolerated dose (MTD) in most patients using this prolonged schedule. Because the initial dose proved to be the MTD on this prolonged schedule, several patients received a starting dose of either 20 mg/m2/day or 18 mg/m2/day. This continuous infusion was administered for at least 21 days or until either the leukocyte count dropped to less than 2,000/mm3, platelets dropped to less than 75,000/mm3, or tumor progression occurred. Plasma etoposide levels were obtained at random times during infusions at 25 mg/m2/day. RESULTS: Duration of therapy ranged from 15-561 days. Myelosuppression was the major toxic reaction, although it was mild in most patients and reduced compared with other schedules. Myelosuppression correlated with the extent of prior treatment: minimally pretreated patients tolerated prolonged infusions with only mild hematologic toxic effects, whereas heavily pretreated patients experienced moderate myelosuppression. Patients treated at an initial dose of 25 mg/m2/day had more myelosuppression than did those treated at 20 mg/m2/day. A leukocyte count of less than 1,000/mm3 developed in only 5 of 40 patients (12%) at any time during therapy. Twenty-one patients required packed erythrocyte transfusions, and one required platelet transfusion. The mean serum etoposide concentration in patients receiving 25 mg/m2/day was 0.7 plus or minus 0.42 microgram/ml. Objective responses were obtained in 5 of 10 patients with previously treated non-Hodgkin's lymphoma and 2 of 3 patients with previously untreated extensive stage small cell lung cancer. CONCLUSIONS: Etoposide administered by continuous infusion can be given at 25 mg/m2/day for prolonged periods to most patients and is the MTD in previously treated patients. Tumoricidal activity in selected tumor types is demonstrated with this dose. Further study in neoplasms that considered "etoposide-sensitive" seems warranted.

Adult↗
PubMed1994

High-dose, brief duration, multiagent chemotherapy for metastatic breast cancer.

BACKGROUND: The authors evaluated a high-intensity inpatient regimen using augmented but subtransplantation doses of multiple agents in patients with metastatic breast cancer. Two high-dose courses were given in an attempt to improve the efficacy of high-dose regimens using a single course. METHODS: Forty women received treatment between October 1988 and October 1991. The median age was 38 years (range, 24-56 years). Twenty-five patients were receiving their first chemotherapy for metastatic disease; 15 patients had received one or more prior regimens. The patients received two courses of chemotherapy, which consisted of the following: cyclophosphamide 1500 mg/m2 intravenously (i.v.) on days 1 and 2; doxorubicin 45 mg/m2 i.v. on days 1 and 2; cisplatin 20 mg/m2 i.v. on days 1, 2, 3, 8, 9, and 10; 5-fluorouracil 1000 mg/m2 on days 8, 9, and 10 (continuous infusion); methotrexate 100 mg/m2 i.v. on days 15 and 22; leucovorin 15 mg/m2 i.v. or by mouth for four doses beginning 24 hours after methotrexate. Etoposide 400 mg/m2 i.v. on days 1, 2, and 3 was substituted for doxorubicin in 14 patients who had received prior doxorubicin. RESULTS: Twenty-nine of 40 patients (73%) had objective response to therapy, with 10 (25%) complete responses. Four patients who obtained a complete response remain disease-free at 14, 21, 28, and 32 months, respectively; all of these patients received this regimen as first-line therapy for metastatic disease. Myelosuppression was severe, with median durations of leukocytes less than 1000/microliters and platelets less than 50,000/microliters of 15 days (range, 7-48 days) and 13 days (range, 3-49 days), respectively. Moderate or severe mucositis occurred in 56 of 68 courses. Four patients (10%) had treatment-related deaths. CONCLUSIONS: This regimen produced high overall response and complete response rates compared with standard regimens. However, only 15% of patients who received this therapy as first-line treatment for metastatic breast cancer remain disease-free, and median response duration was shorter than that reported using high-dose therapy with bone marrow support. Toxicity with this regimen was greater than anticipated, although myelosuppression and stomatitis would be reduced by the use of cytokines. This regimen does not improve results achieved with standard therapy sufficiently to justify its toxicity and expense.

Adult↗
PubMed1994

Prolonged administration of low-daily-dose etoposide: a superior dosing schedule?

Despite the clinical use of etoposide for about 20 years, the best dose and schedule of administration remains unknown. The schedule dependency for small-cell lung cancer (SCLC) has been unequivocally demonstrated, and it is probably similar for other sensitive neoplasms (for example, lymphoma, germ cell tumors). A more extended schedule of administration (i.e., 14-21 days) may be more effective than the standard 3- to 5-day schedule. Plasma levels in reference to dose, schedule, and tumor responsiveness have been evaluated in several studies. These data suggest that high peak levels (i.e., > 5-10 micrograms/ml) are most often associated with more severe myelosuppression than are lower peak plasma levels (i.e., 1-3 micrograms/ml). In SCLC patients the response rates and survival observed following the administration of low daily etoposide doses for 14-21 days are similar to the results achieved with standard doses given for 3-5 days. These data as well as other studies suggest that giving low daily doses of etoposide on a prolonged schedule is superior. Randomized comparisons are necessary for an unequivocal confirmation of these observations.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Practical approaches to the treatment of patients with extensive stage small cell lung cancer.

Although initially extremely sensitive to many chemotherapeutic drugs and radiotherapy, ultimately small cell lung cancer (SCLC) is a progressive and fatal disease. Stage of disease is a major prognostic factor in the treatment of SCLC patients. Patients with limited stage disease have approximately a 10% chance of long-term (> 5 years) disease-free survival, whereas those with extensive stage disease are incurable with currently available therapy. In extensive stage disease, patients with a good performance status and younger than 65 years of age are ideal candidates for trials using intensive standard chemotherapy or experimental modalities; most patients, however, including those who are elderly and medically unfit, are best treated conservatively with single-agent etoposide. Various types of therapy, including intensive induction chemotherapy and consolidation regimens, have been unable to improve survival rates in extensive stage SCLC. Thus, until better treatments are developed, the goal of therapy for extensive stage SCLC should be adequate palliation and prolongation of quality survival.

Aged↗
PubMed1994

Paclitaxel (Taxol): phase I/II trial comparing 1-hour infusion schedules.

This phase I/II study was done to evaluate the safety and feasibility of two schedules of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered by 1-hour infusion in the outpatient setting. Fifty-six patients with advanced, refractory malignancies received one of two paclitaxel schedules by random assignment: 135 mg/m2 given as a single dose over 1 hour or 135 mg/m2 given in divided hourly daily doses for 3 days. All patients were premedicated with dexamethasone, diphenhydramine, and cimetidine. No serious acute hypersensitivity reactions were seen with either schedule of paclitaxel. Other adverse effects were usually mild and easily tolerated. Other than alopecia, which was universal, myelosuppression was the most common severe toxicity. However, grades 3 and 4 leukopenia occurred in only 19% and 2% of treatment courses, respectively. Nine patients required hospitalization for treatment of fever associated with neutropenia. There were no significant differences in toxicity observed when comparing the two paclitaxel regimens. It is too early to adequately assess tumor response, but thus far 11 of 56 patients (20%) had partial or complete response to therapy. Responses were observed in patients with breast, ovarian, and lung cancers. Paclitaxel can be safely given by 1-hour infusion in the outpatient setting, both as a single dose and in divided doses for 3 days. Severe acute hypersensitivity reactions did not occur in 162 courses. Neutropenia was mild in most patients and severe thrombocytopenia was rare. The use of this dose and these schedules of paclitaxel as a component of combination chemotherapy regimens should be possible. Investigation of paclitaxel at 200 mg/m2 given by 1-hour infusion is currently in progress.

Adult↗
PubMed1994

Poorly differentiated carcinoma or adenocarcinoma of unknown primary site: long-term results with cisplatin-based chemotherapy.

Cases of poorly differentiated carcinoma and poorly differentiated adenocarcinoma of unknown primary site represent a large minority of patients with carcinoma of unknown primary site and are clinically distinct in several ways from well-differentiated adenocarcinoma. Cisplatin-based combination chemotherapy produces meaningful clinical responses in more than 50% of the poorly differentiated histologies, and there is a potential for cure in some of these patients (10% to 15%). Clinical and pathologic features enable us to identify many of the patients with responsive tumor types. It is hoped that the future will brighten for these patients as the prospects of genetic diagnosis and treatment become more realistic, and the therapy of common epithelial neoplasms becomes more successful.

Adenocarcinoma↗
PubMed1993

Chronic etoposide administration: overview of clinical experience.

Etoposide is an important anti-neoplastic drug, but the best dose and schedule for its administration remain unknown. The schedule-dependency of etoposide for small cell lung cancer (SCLC) is now proven and it is probably true for other sensitive neoplasms as well (e.g., lymphoma and germ cell tumors). Recent data suggest that an extended schedule of administration (i.e., 14 to 21 days) may be more effective than the standard 3- to 5-day schedule. Several phase II studies with etoposide have demonstrated its activity against several neoplasms. Some have assessed the relationship of etoposide plasma levels to dose, schedule, and tumor responsiveness. Preliminary data suggest that high peak plasma levels (i.e., > 5 to 10 micrograms/ml) are associated with more severe myelosuppression than lower peak plasma levels (i.e., 1 to 3 micrograms/ml). Response and survival rates in previously untreated SCLC patients given low daily doses of etoposide for 14 to 21 days are at least comparable with results achieved with standard etoposide doses given for 3 to 5 days, and the extended etoposide schedule is less toxic than the 3- to 5-day schedule. Preliminary data from several studies suggest that administering low, daily etoposide doses over a prolonged schedule is a superior method of administration. Other studies, including randomized comparisons, are necessary to confirm these observations.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Bioavailability of low-dose oral etoposide.

PURPOSE: To determine the bioavailability of oral etoposide capsules administered at doses of 100 mg and 400 mg. PATIENTS AND METHODS: The bioavailability of oral etoposide was determined by measuring the area under the etoposide plasma concentration versus time curve (AUC) following intravenous (IV) etoposide administration and comparing that value to the AUC achieved following an oral dose administered 1 day later to the same patient. The bioavailability of a 100-mg oral dose of etoposide was measured on 16 occasions in 11 patients. The bioavailability of a 400-mg dose was determined on 12 occasions in six patients. RESULTS: The mean (+/- SD) bioavailability following a 100-mg dose of oral etoposide was 76% +/- 22%, which was significantly greater (P < .01) than the mean bioavailability of 48% +/- 18% following a 400-mg oral dose. The coefficient of variation in oral etoposide bioavailability was significant: 29% with a 100-mg oral dose and 37% with a 400-mg dose. CONCLUSION: Bioavailability of a 100-mg oral etoposide dose is greater than suggested in the package insert from Bristol Laboratories (Evansville, IN). Comparable oral etoposide doses are not uniformly twice that of an IV dose, as suggested by the package insert, but will depend on the final oral dose administered. Bioavailability is better at lower oral etoposide doses. This study confirms the wide interpatient and intrapatient variability in oral etoposide bioavailability.

Administration, Oral↗
PubMed1993

Effective therapy for poor-prognosis non-Hodgkin's lymphoma with 8 weeks of high-dose-intensity combination chemotherapy.

PURPOSE: Despite substantial advances in the treatment of aggressive non-Hodgkin's lymphoma, therapeutic results with conventional regimens remain poor in some subsets of patients. In an attempt to improve the prognosis of such patients we used an 8-week, multidrug chemotherapy regimen of high dose-intensity. PATIENTS AND METHODS: Between April 1986 and April 1991, 70 patients with advanced intermediate- or high-grade non-Hodgkin's lymphoma were treated. The median age was 41 years (range, 18 to 69). Fifty-one patients (73%) had stage IV disease; 37 (53%) were Shipp's category 3; 17 (24%) had small noncleaved-cell lymphoma; 35 (50%) had Eastern Cooperative Oncology Group (ECOG) performance status > or = 2; 24 (34%) had two or more extranodal sites involved; and 17 (24%) had bone marrow involvement. The 8-week regimen included cyclophosphamide, etoposide, doxorubicin, vincristine, bleomycin, methotrexate with leucovorin rescue, and prednisone. RESULTS: Sixty-two of 70 patients completed the regimen as planned. Fifty-seven patients (81%) obtained a complete response (CR) and the actuarial 5-year failure-free survival rate is 52%. Thirty-seven patients remain alive and disease-free a median of 35 months (range, 7 to 68) after therapy. Adverse prognostic factors included age more than 50 years, bone marrow involvement, and serum lactic dehydrogenase (LDH) more than 500 IU/L (normal range, 125 to 250). Myelosuppression was responsible for most of the treatment-related toxicity. Severe leukopenia (< 1,000/microL) occurred in all patients and lasted a median of 9 days. Seven patients (10%) died of myelosuppression-related complications; five of these patients were older than 60 years. CONCLUSION: This brief but intensive therapy was effective in treating poor-prognosis patients with non-Hodgkin's lymphoma. With this therapy, patients with small noncleaved-cell lymphoma or Shipp's category 3 disease had treatment outcome similar to the group as a whole. This therapy was not well tolerated by patients older than 60 years, and should not be given to this subgroup. Verification of these results in a randomized trial setting is indicated.

Adolescent↗
PubMed1993

Combination chemotherapy with or without thoracic radiotherapy in limited-stage small-cell lung cancer: a randomized trial of the Southeastern Cancer Study Group.

PURPOSE: The primary objective of this randomized prospective study was to compare the survival of limited-stage small-cell lung cancer (SCLC) patients treated with chemotherapy alone or chemotherapy plus thoracic radiotherapy (TRT). A secondary objective was to determine the effect of consolidation chemotherapy on survival. PATIENTS AND METHODS: This multiinstitutional phase III study included 386 patients with limited-stage SCLC. All patients received cyclophosphamide 1,000 mg/m2, doxorubicin 40 mg/m2, and vincristine 1 mg/m2 (CAV) every 3 weeks for six cycles. Irradiated patients received 30 Gy in 10 fractions during weeks 1 and 2 of chemotherapy. Fifteen Gy in five fractions was administered during week 7 (total dose, 45 Gy). Following CAV, responding patients were randomized to receive two cycles of consolidation chemotherapy (cisplatin 20 mg/m2/d for 4 days plus etoposide 100 mg/m2/d for 4 days) or observation. RESULTS: Complete (46% and 38%; P = .14) and overall response rates (67% and 64%; P = .58) were not statistically significantly different. Although not significantly different, median (14.4 v 12.8 months) and 2-year survival (33% v 23.5%) rates favored the irradiated patients. Grade 4 hematologic toxicity was greater in irradiated patients (60% and 39%; P < .001). Patients given consolidation chemotherapy experienced superior median (21.1 v 13.2 months; P = .028) and 2-year survival (44% v 26%; P = .028) rates. CONCLUSION: The concurrent use of TRT and CAV chemotherapy as administered in this study failed to improve the survival of limited-stage SCLC patients compared with CAV alone. Life-threatening hematologic toxicities were more frequent with combined-modality therapy. The survival of limited-stage patients treated with CAV (with or without TRT) was improved with two cycles of cisplatin and etoposide consolidation therapy. Whether similar survival results could be achieved with cisplatin and etoposide alone requires additional study.

Adult↗
PubMed1993

Prolonged administration of low-dose, infusional etoposide in patients with etoposide-sensitive neoplasms: a phase I/II study.

PURPOSE: This trial evaluated the activity and toxicity of a prolonged schedule of low-dose, daily infusional etoposide in patients with etoposide-sensitive neoplasms. PATIENTS AND METHODS: Fifteen patients (non-Hodgkin's lymphoma, n = 10; small-cell lung cancer, n = 3; germ cell neoplasm, n = 2) were treated. Ten had received etoposide previously. Etoposide 18 to 25 mg/m2/d was administered by continuous intravenous infusion for at least 21 days, or until either leukocyte count decreased to less than 2,000/microL, platelets decreased to less than 75,000/microL, or tumor progressed. Plasma etoposide levels were monitored during infusion. RESULTS: Duration of therapy ranged from 21 to 560 days; uninterrupted infusion ranged from 21 to 153 days. Seven patients (47%) had an objective tumor response (six partial, one complete), with a median duration of 7 months (range, 2 to 19). Myelosuppression limited the infusion; however, only four patients had grade 4 leukopenia, and most tolerated infusions with mild to moderate leukopenia. Nine patients required RBC transfusions. Only one patient developed severe thrombocytopenia. Alopecia was universal; however, other grade 3 or 4 nonhematologic toxicities were not encountered. The mean serum etoposide concentration was 0.7 +/- 0.42 microgram/mL. Only three patients had serum etoposide levels greater than 1 microgram/mL. CONCLUSION: Etoposide administered as a low-dose continuous infusion is active in etoposide-sensitive neoplasms. Myelosuppression is the major toxicity, but seems reduced when compared with other schedules. Tumor cytotoxicity was demonstrated with plasma levels ranging from 0.5 to 1.0 microgram/mL. Chronic low doses of etoposide may be superior to the standard dose and schedule and further study of this issue is warranted.

Adult↗
PubMed1993

Treatment of poor prognosis non-Hodgkin's lymphoma with intensive, inpatient combination chemotherapy of brief duration: long-term followup.

Between 1982 and 1990, we treated patients with poor prognosis non-Hodgkin's lymphoma (NHL) with inpatient, dose-intensive multidrug chemotherapy. Dose intensity was approximately 2.6 times that of the standard CHOP regimen. All patients had intermediate or high grade NHL, as well as one or more clinical features predictive of poor prognosis. Initial results were previously reported in a group of 56 patients, and in a subgroup of 20 patients with small noncleaved cell lymphoma. In this report, we present long-term followup of the patients previously reported. Median follow up is now 75 months (range 48-122 months). Since our initial reports, the survival curves have remained essentially unchanged, with an actuarial 5 year survival of 48% for the entire group and 60% for the patients with small noncleaved cell lymphoma. Disease-free survival is 42% for patients in Shipp's category 3. Three late relapses occurred, all > 36 months after treatment. No late toxicities or second malignancies have been observed. Intensive, short duration therapy is feasible and effective, and may provide particular advantage to patients with small noncleaved cell histology or other poor prognostic features. Exploration of the importance of dose intensity in lymphoma treatment should continue; comparison of this regimen with standard CHOP is indicated.

Adolescent↗