melphalan and Vomiting

Intra-arterial chemotherapy is a new retinoblastoma treatment associated with high rates of globe salvage that has been widely adopted for primary treatment of retinoblastoma but is less frequently used as secondary treatment for refractory retinoblastoma. This systematic review aims to summarize the reported outcomes of intra-arterial chemotherapy for refractory retinoblastoma.. We conducted a systematic review of studies published on PubMed, Medline, and Embase from 2011 to 2021 reporting globe salvage rates following intra-arterial chemotherapy for secondary treatment of refractory retinoblastoma.. Our search yielded 316 studies, and 24 met inclusion criteria. The 24 included studies were comprised of 1366 patients and 1757 eyes. Among these, 1184 (67%) eyes received secondary indication treatment, and globe salvage was achieved for 776 of these 1184 eyes (64%). Sixteen studies reported cannulation success rates from 71.8 to 100%. Pooled analysis of subjects revealed 21 patients (2.6%) with metastatic disease and 26 deaths (3%) during study follow-up periods (7-74 months). The most common ocular complications were vitreous hemorrhage (13.2%), loss of eyelashes (12.7%), and periocular edema (10.5%). The most common systemic complications were nausea/vomiting (20.5%), neutropenia (14.1%), fever (8.2%), and bronchospasm (6.2%).. Intra-arterial chemotherapy is associated with high rates of globe salvage and low rates of serious complications in patients with refractory retinoblastoma. Unfortunately, current literature is predominantly comprised of retrospective case studies, and further high-quality evidence is necessary to inform clinical practice.

Topics: Antineoplastic Agents; Bronchial Spasm; Carboplatin; Drug Resistance, Neoplasm; Edema; Eyelashes; Febrile Neutropenia; Humans; Infusions, Intra-Arterial; Melphalan; Methotrexate; Nausea; Retinal Neoplasms; Retinoblastoma; Salvage Therapy; Topotecan; Vitreous Hemorrhage; Vomiting

High-dose melphalan (HDMel) is the most common conditioning chemotherapy regimen for autologous stem cell transplantation (SCT) in patients affected by multiple myeloma (MM). No consensus exists for the emetogenicity or prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in this regimen.. Data on the incidence and efficacy/safety of CINV prophylaxis among patients affected by MM undergoing autologous SCT with the HDMel regimen was extracted from electronic databases and analyzed.. Eleven studies involving multiple CINV prophylaxis regimens were identified and included. No consensus on HDMel emetogenicity was reached, but most studies summarized the emetogenicity as moderate-high risk. An aprepitant-based three-drug regimen (aprepitant + serotonin receptor antagonist (5HT3RA) + dexamethasone) showed better efficacy than a two-drug regimen (5HT3RA + dexamethasone) for CINV prevention without increasing the frequency in adverse events.. The aprepitant-based three-drug regimen should be the regimen of choice for CINV prophylaxis for MM patients undergoing autologous SCT with HDMel conditioning.

Topics: Adult; Antiemetics; Antineoplastic Agents, Alkylating; Aprepitant; Dexamethasone; Female; Hematopoietic Stem Cell Transplantation; Humans; Induction Chemotherapy; Male; Melphalan; Multiple Myeloma; Nausea; Quality of Life; Serotonin Antagonists; Transplantation Conditioning; Transplantation, Autologous; Vomiting

Topics: Adrenal Cortex Hormones; Animals; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Breast Neoplasms; Cyclophosphamide; Dacarbazine; Doxorubicin; Drug Therapy, Combination; Dyspnea; Fluorouracil; Hodgkin Disease; Humans; Hypercalcemia; Leukemia; Leukemia, Lymphoid; Lymphoma; Mechlorethamine; Melphalan; Methotrexate; Multiple Myeloma; Palliative Care; Prednisone; Procarbazine; Receptors, Glucocorticoid; Vinblastine; Vincristine; Vomiting

Evidence supports olanzapine for prophylaxis of chemotherapy-induced nausea/vomiting (CINV) for highly emetogenic chemotherapy; however, most studies focus on solid malignancies and single-day regimens. A randomized, double-blinded, placebo-controlled trial was conducted to compare the addition of olanzapine to triplet therapy (fosaprepitant, ondansetron, dexamethasone [FOND-O]) versus triplet therapy alone (FOND) in preventing CINV in hematology patients receiving single-day and multiple-day highly emetogenic chemotherapy and hematopoietic cell transplant (HCT) regimens (NCT02635984). The primary objective of this study was to compare complete response (CR; no emesis and minimal nausea, <25 mm on a 100-mm visual analog scale) during the overall assessment period (chemotherapy days plus 5 days after). Secondary objectives were the number of emesis, number of rescue medications, percent achieving minimal nausea, and percent achieving complete protection (CP; no emesis, rescue antiemetic, or significant nausea), all of which are reported as acute (chemotherapy days), delayed (5 days after chemotherapy), and overall phases. Olanzapine 10 mg or matching placebo were given on each chemotherapy day and 3 days after. Adults with hematologic malignancy receiving HCT regimens of melphalan, BEAM (carmustine, etoposide, cytarabine, melphalan), busulfan (Bu)/cyclophosphamide (Cy), Bu/fludarabine (Flu), Bu/melphalan, FluCy, FluCy-total body irradiation (TBI), etoposide-TBI, and ICE (ifosfamide, carboplatin, etoposide) or 7+3 chemotherapy regimens were included. An estimated 98 patients were required using alpha = .05 and 80% power. No significant differences existed in baseline characteristics between FOND-O (n = 51) and FOND (n = 50) arms. Mean duration of olanzapine was 7.7 days (range, 4 to 11). Discontinuation for possible adverse events occurred in 3 placebo and 0 olanzapine patients. CR was significantly higher for FOND-O in overall (55% versus 26%, P = .003) and delayed (60.8% versus 30%, P = .001) but not acute (P = .13) phases. Significantly more patients receiving FOND-O achieved no more than minimal nausea in overall (P = .001) and delayed phases (P = .0002), as well as fewer overall mean emesis counts (P = .005). CP rates were not different in any assessment phase (P ≥ .05 each). Within the HCT subgroup (n = 64), the CR, CP, and no significant nausea rates were significantly better for FONDO-O in overall and delayed phases (all P < .05). Analysis within th

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Induction Chemotherapy; Male; Melphalan; Middle Aged; Morpholines; Nausea; Olanzapine; Ondansetron; Podophyllotoxin; Vomiting

This phase II trial evaluates, for the first time, the safety and efficacy of bendamustine plus high-dose melphalan (HDM) as a conditioning regimen before the second autologous stem cell transplantation (ASCT) in previously untreated multiple myeloma (MM) patients. In total, 32 ASCT patients received HDM (200 mg/m(2)) as conditioning for the first ASCT. After 3-6 months from the first ASCT, responding patients underwent a second ASCT following bendamustine (200 mg/m(2)) and HDM (140 mg/m(2)). High-dose chemotherapy and ASCT were performed with complete neutrophil and platelet recovery in all patients. The median number of days to neutrophil and platelet engraftment was 11 (range 9-15) and 12 (range 10-19), respectively. Only one subject experienced grade 3 diarrhea; the rate of mucositis and vomiting was significantly lower with the bendamustine plus HDM regimen compared with the HDM-only regimen (81.2 vs 96.9%, P=0.025 and 78.1 vs 100%, P=0.008). Overall response rate (ORR) was 81.2% after the first transplant, and 90.6% after the second, while complete response rates were 46.8 and 62.5%, respectively (P=0.016). Actuarial 2-year PFS and OS were 79% (95% confidence interval (CI), 60-98) and 97% (95% CI, 91-100), respectively. Bendamustine+HDM is feasible as the conditioning regimen for second ASCT in MM patients. The present study may pave the way for phase III studies specifically aimed at further investigating this combination strategy. The role of this combination in MM for conditioning regimen in a first or single ASCT setting should be also investigated.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bendamustine Hydrochloride; Diarrhea; Female; Graft Survival; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Mucositis; Multiple Myeloma; Transplantation Conditioning; Treatment Outcome; Vomiting

The aim of this study is to evaluate the efficacy of aprepitant as part of the antiemetic regimen for high-dose melphalan conditioning in multiple myeloma patients.. This is a prospective, single-arm study.. The study was conducted at an Academic Medical Facility.. Twenty-six patients receiving high-dose melphalan with autologous stem cell support were included in this study.. Eligible patients were >18 years with a diagnosis of MM undergoing high-dose melphalan followed by autologous peripheral blood stem cell transplantation (PBSCT). All patients had serum aminotransferases and total bilirubin less than 2× upper limit of normal. Treatment consisted of aprepitant 125 mg orally on day 1, followed by 80 mg orally 24 and 48 h after the initial dose; ondansetron 16 mg orally day 1; dexamethasone 12 mg orally day 1, and 8 mg orally days 2-4 with breakthrough medications as needed.. Patients were evaluated for the frequency of emetic episodes, the need for breakthrough antiemetic medication, and the mean nausea score in 24-h increments beginning 24 h after chemotherapy and continuing until 120 h. Nausea score was determined using a linear analog scale (0-10). Complete response (CR) was defined as no more than one (1) emetic episode during the evaluation period. A total of 26 patients (17 male, 9 female) were enrolled in the study. Of these, 25 (96 %) were complete responders and 24 (92 %) had no documented emetic episodes during the study period. One patient (4 %) had 1 emetic episode and one patient (4 %) had 2 emetic episodes. Some degree of nausea was reported by 23/26 patients, and the mean nausea score for the entire group over the study period was 0.7 (range 0-10).. Addition of aprepitant to standard antiemetics resulted in low rates of delayed nausea/vomiting associated with high-dose melphalan and PBSCT, and has now become standard practice in this patient population at our institution.

Topics: Antiemetics; Aprepitant; Female; Humans; Male; Melphalan; Middle Aged; Morpholines; Multiple Myeloma; Nausea; Peripheral Blood Stem Cell Transplantation; Prospective Studies; Transplantation Conditioning; Vomiting

The optimal regimen to prevent chemotherapy-induced nausea and vomiting (CINV) for patients undergoing high-dose chemotherapy and autologous stem-cell transplantation (ASCT) is unclear. To evaluate the effect of aprepitant in addition to a standard regimen, we conducted this randomized, placebo-controlled phase III trial.. Patients with multiple myeloma were randomly assigned at a one-to-one ratio to receive either aprepitant (125 mg orally on day 1 and 80 mg orally on days 2 to 4), granisetron (2 mg orally on days 1 to 4), and dexamethasone (4 mg orally on day 1 and 2 mg orally on days 2 to 3) or matching placebo, granisetron (2 mg orally on days 1 to 4), and dexamethasone (8 mg orally on day 1 and 4 mg orally on days 2 to 3). Melphalan 100 mg/m(2) was administered intravenously on days 1 to 2. ASCT was performed on day 4. The primary end point (complete response) was defined as no emesis and no rescue therapy within 120 hours of melphalan administration. Quality of life was assessed by modified Functional Living Index-Emesis (FLIE) questionnaire on days -1 and 6.. Overall, 362 patients were available for the efficacy analysis (181 in each treatment arm). Significantly more patients receiving aprepitant reached the primary end point (58% v 41%; odds ratio [OR], 1.92; 95% CI, 1.23 to 3.00; P = .0042). Absence of major nausea (94% v 88%; OR, 2.37; 95% CI, 1.09 to 5.15; P = .026) and emesis (78% v 65%; OR, 1.99; 95% CI, 1.25 to 3.18; P = .0036) within 120 hours was increased by aprepitant. Mean total FLIE score (± standard deviation) was 114 ± 18 for aprepitant and 106 ± 26 for placebo (P < .001).. The addition of aprepitant resulted in significantly less CINV and had a positive effect on quality of life.

Topics: Aprepitant; Dexamethasone; Double-Blind Method; Granisetron; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Morpholines; Multiple Myeloma; Nausea; Prospective Studies; Quality of Life; Transplantation, Autologous; Vomiting

Complete protection from nausea/vomiting is currently achieved in a minority of patients receiving high-dose chemotherapy (HDC). Currently the use of 5-HT3-antagonists and dexamethasone (DEX) represents the standard of care. The role of the NK-1-antagonist aprepitant in HDC remains to be better defined. A total of 64 patients undergoing multiple days of HDC received granisetron, DEX plus aprepitant during chemotherapy. After the end of chemotherapy aprepitant plus DEX was given for a further 2 days. Primary end point was CR defined as no vomiting and no use of rescue medication in the overall phase (day 1 until 5 days after end of chemotherapy). Acute/delayed and overall CR were achieved in 83%/70% and 63%, respectively. Acute and delayed nausea were observed in 20 and 38% of the patients. The tolerability of the aprepitant regimen over 4-5 days was comparable with the 3-day antiemetic regimen. In our study, aprepitant demonstrated good tolerability. Taking into account the methodological constraints of comparing our results with those from the available literature, the addition of aprepitant to the antiemetic treatment regimen may provide improved prevention of chemotherapy-induced nausea and vomiting during HDC.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Etoposide; Female; Granisetron; Humans; Ifosfamide; Male; Melphalan; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Paclitaxel; Treatment Outcome; Vomiting; Young Adult

Explore safety and efficacy of three palonosetron-containing regimens for emesis prevention over 7 days in multiple myeloma (MM) patients receiving melphalan (100 mg/m(2)) and hematopoietic stem cell transplantation (HSCT).. Randomized, double-blind pilot study in MM patients (n=73) receiving 1, 2, or 3 days of 0.25 mg palonosetron (30-s i.v. bolus) 30 min before melphalan (days -2 and -1) and HSCT (day 0). Patients received dexamethasone (20 mg i.v., days -2 and -1) immediately before or after study drug/placebo. Daily diaries recorded emesis, rescue medication, nausea duration, and adverse events (AEs).. Seven-day complete protection (no emesis) occurred in 41.7% [95% confidence interval (CI) 22.1% to 63.4%], 41.7% (95% CI 22.1% to 63.4%), and 44.0% (95% CI 24.2% to 65.1%) of patients receiving 1, 2, or 3 days of palonosetron, respectively (P=0.43). Complete response (emesis free without rescue medication) occurred in 8.3%, 20.8%, and 20.0% (P=0.14). Common AEs (≥10%) were mild-to-moderate diarrhea, constipation, headache, insomnia, and flatulence. No serious AEs occurred.. Palonosetron with dexamethasone was safe and effective in preventing emesis in MM patients receiving melphalan and HSCT. This pilot study with a limited number of patients suggests that multiple doses of palonosetron could be more effective than a single dose in making patients emesis free without need for rescue medication. However, even multiple doses of palonosetron resulted in only 20% of patients being emesis free without rescue medication, suggesting that further improvement will require development of more effective combination antiemetic therapy.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Dexamethasone; Double-Blind Method; Female; Hematopoietic Stem Cell Transplantation; Humans; Isoquinolines; Male; Melphalan; Middle Aged; Multiple Myeloma; Nausea; Palonosetron; Quinuclidines; Vomiting

We performed a clinical study of a triple-drug combination to evaluate its efficacy to prevent both acute and delayed emesis after high-dose chemotherapy with BEAM (BCNU [carmustine]+etoposide+ARA-C [cytarabine]+melphalan) before hematopoietic stem cell transplantation (HSCT) by comparison with a historical control group of patients treated with dexamethasone (dex) and ondansetron or palonosetron.. We evaluated 96 patients non-Hodgkin's lymphomas (n=54), and Hodgkin's disease (n=42). Evaluated patients received: aprepitant+palonosetron and dex. The observation period started with the initiation of chemotherapy (0 hours) and continued for 24 hours after the completion of the chemotherapy for the acute phase, and during 5 days after finishing chemotherapy for the delayed phase. The response rate to study drugs was evaluated using a four-grade scale based on the degree of control of nausea and vomiting: high, modrate, slightly effective, or not effective.. Patients treated with the three-drug combination showed a significantly higher response rate than those receiving palonosetron or ondasetron (+dex) during the both the acute and the delayed phases: highly effective early+late phases, 82% versus 70% versus 35%; highly effective early phase, 94% versus 70% versus 35%; highly effective late phase, 85% versus 85% versus 50%; highly+moderately effective early phase, 97% versus 70% versus 40%; highly+moderately effective late phase, 97% versus 90% versus 60%, for triple combination, palonosctron with dexamethasone and ondasetron+dex, respectively. All antiemetic regimens were well tolerated. The three-drug combination showed a similar safety profile; adverse events were generally mild and transient.. The triple-drug combination was more effective than ondansetron or palonosetron (+dex) treatments to prevent acute (especially) and delayed nausea and vomiting following BEAM before HSCT.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carmustine; Cytarabine; Dexamethasone; Drug Therapy, Combination; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Isoquinolines; Lymphoma, Non-Hodgkin; Male; Melphalan; Morpholines; Nausea; Ondansetron; Palonosetron; Quinuclidines; Transplantation, Autologous; Treatment Outcome; Vomiting

Amifostine (WR-2721; Ethyol) is a well-known cytoprotector, but a possible role in preventing extrahaematological toxicity after high-dose therapy (HDT) has never been investigated. We compared two historical groups of patients who either received (group A, n = 35) or did not receive (group B, n = 33) amifostine (740 mg/m2) before high-dose (HD) melphalan, followed by autologous infusion of peripheral blood progenitor cells (PBPCs). Amifostine was well tolerated at this dose level. Emesis grade 1-2 was the most important side-effect, but the interruption of infusion was never required. The incidence and median duration of severe mucositis (grade 3-4) was 21% and 0 d (range 0-11 d) in group A and 53% and 7 d (range 0-11 d) in group B. The duration of analgesic therapy was also significantly lower in group A (0 d; range 0-12) than in group B (6 d, range 0-20) (P = 0.0001). Severe diarrhoea (3% vs. 25%; P = 0.01) and emesis (9% vs. 34%; P = 0.01) were also reduced in group A in comparison with group B. No differences were observed between the two groups for haematological recovery. This retrospective study strongly suggests that amifostine can reduce severe mucositis and the use of analgesic drugs in this setting. A randomized study is warranted to confirm these preliminary results.

Topics: Adolescent; Adult; Aged; Amifostine; Analgesics, Opioid; Antineoplastic Agents, Alkylating; Blood Cell Count; Diarrhea; Drug Therapy, Combination; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Mouth Mucosa; Pain; Radiation-Protective Agents; Retrospective Studies; Stomatitis; Treatment Outcome; Vomiting

The aim of this study was to compare antiemetic efficacy of three serotonin antagonists, granisetron, tropisetron and ondansetron, during conditioning for autologous stem cell transplantation (ASCT). Forty-five malignant lymphoma patients (mean age 38 years, M:F 30:15), undergoing the highly emetogenic regimen BEAM prior to ASCT, were randomized to receive IV granisetron (G) 3 mg once a day, IV tropisetron (T) 5 mg once a day, or IV ondansetron (0) 8 mg twice daily, for six days. The treatment groups were comparable with respect to age, sex and previous experience of nausea and/or vomiting. Nausea and/or emesis control failure was defined as a nausea lasting > or = 4 hours and/or > or = 3 episodes of vomiting/24 h, emesis control failure as > or = 3 episodes of vomiting/24 h. Both the period of chemotherapy (6 days) and the whole period of observation (10 days) were evaluated. Nausea and/or emesis control failure occurred in 24% of patients during the period of chemotherapy and in 51% of patients throughout the whole period of observation, while emesis control failed in 2% and 27% of patients, respectively. The efficacy of three serotonin antagonists was comparable during the chemotherapy period (5 patients with nausea and/or emesis control failure in the granisetron group, 2 in the tropisetron group and 4 in the ondansetron group,p = 0.40). When evaluating the whole period of observation, the antiemetic response to G and T was significantly better than to O, nausea and/or emesis control failure having occurred in 7 (47%) patients treated with G, 5 (33%) patients treated with T, and 12 (80%) patients treated with O, p = 0.03. The results concerning emesis control failures were similar, G 4 (27%), T 1 (7%), O 7 (47%), p = 0.04. Headache was the only frequent side effect of serotonin antagonists (30% incidence). All three serotonin antagonists sufficiently controlled nausea and vomiting during high-dose chemotherapy (BEAM) administration in 67-87% of patients. In comparison with ondansetron, both tropisetron and granisetron proved to be more effective after ASCT, when emetogenic factors other than chemotherapy alone participated.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Combined Modality Therapy; Cytarabine; Etoposide; Female; Granisetron; Hematopoietic Stem Cell Transplantation; Humans; Indoles; Lymphoma; Male; Melphalan; Nausea; Ondansetron; Serotonin Antagonists; Transplantation, Autologous; Tropisetron; Vomiting

One hundred and eleven patients receiving conditioning regimens for hematopoietic stem cell transplantation (HSCT) were administered a single intravenous dose (40 micrograms/kg) of granisetron before chemo-radio therapy. The efficacy of the drug was assessed every 24 hours, rating the control of nausea and vomiting as complete, major, minor or failure. On day 1, 23 of 48 patients (47.9%) who received cyclophosphamide (60 mg/kg/day), achieved control of emesis with complete or major response. On day 2, 17 of 47 patients (36.2%) achieved control emesis. During total body irradiation (TBI) (10 approximately 12 Gy/2 approximately 3 days), 21 of 33 patients (63.6%) achieved control of emesis on day 1 and 22 of 32 patients (68.6%) achieved control of emesis on day 2. During melphalan administration (60 approximately 100 mg/m2/day), 20 of 28 patients (71.4%) achieved control of emesis on day 1. Adverse effects were observed in seven patients but were not serious. We concluded that granisetron has a major role in preparation for HSCT.

Topics: Adolescent; Adult; Antiemetics; Busulfan; Child; Child, Preschool; Cyclophosphamide; Female; Granisetron; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Infant; Male; Melphalan; Middle Aged; Nausea; Serotonin Antagonists; Transplantation Conditioning; Vomiting; Whole-Body Irradiation

The anti-emetic efficacy of a combination of tropisetron and dexamethasone was studied in 33 patients who underwent bone marrow transplantation. Another 50 patients receiving conventional anti-emetic therapies in bone marrow transplantation served as control. On the first and second days of preconditioning chemotherapy, 51% and 36% respectively of patients in the tropisetron and dexamethasone group did not experience vomiting, compared with only 12% and 10% of control group patients (P < 0.001). The mean number of episodes of vomiting in the tropisetron and dexamethasone group was also significantly lower than in the control group (0.97+/-1.65 vs 3.50+/-2.45 and 1.30+/-1.40 vs 4.44+/-2.91 respectively, both P < 0.001). Control of vomiting in the two groups was not significantly different during days 3-6. Analysis of patients receiving busulfan and cyclophosphamide as the preconditioning regimen still showed better anti-emetic control in the tropisetron and dexamethasone group than in the control group on the first two days of treatment (total control rate 33.3% vs 6.5% and 44.4% vs 12.9% respectively, P < 0.001). Patients given tropisetron and dexamethasone combination more frequently suffered from dizziness and burning sensation of the chest. However, diarrhea and extrapyramidal symptoms were the most frequent adverse effects seen after using conventional anti-emetic combination. The combination of tropisetron and dexamethasone was thus superior to conventional anti-emetic combinations in preventing vomiting during preconditioning period of bone marrow transplantation. The adverse effects of this combination were minimal and well tolerated by patients.

Topics: Adolescent; Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Busulfan; Carmustine; Child; Cyclophosphamide; Cytarabine; Dexamethasone; Dizziness; Drug Therapy, Combination; Female; Headache; Heartburn; Humans; Indoles; Leukemia; Male; Melphalan; Middle Aged; Multiple Myeloma; Podophyllotoxin; Transplantation Conditioning; Tropisetron; Vomiting; Whole-Body Irradiation

To evaluate the biologic interactions and toxicities of melphalan (L-PAM) combined with 41.8 degrees C whole-body hyperthermia (WBH) for 60 minutes.. Sixteen patients with refractory cancer were treated (May 1992 to May 1995) with WBH alone during week 1) thereafter patients were randomized to receive either L-PAM alone on week 2 and L-PAM plus WBH on week 5, or the reverse sequence. Patients who demonstrated clinical improvement received WBH plus L-PAM monthly. Dose levels of L-PAM were 10 mg/m2 (n = 3), 15 mg/m2 (n = 3), 17.5 mg/m2 (n = 6), and 20 mg/m2 (n = 4). L-PAM was administered at target temperature; WBH was administered with an Aquatherm radiant-heat device (patent pending; Cancer Research Institute, New York, NY).. Comparisons of mean WBC count and platelet nadirs for L-PAM alone and L-PAM plus WBH demonstrated that the addition of WBH resulted in nadir counts that were, on average, 25% lower. There were no instances of febrile neutropenia or bleeding. Toxicities allowed for escalation of L-PAM to 20 mg/m2; all four patients at this level experienced grade 4 myelosuppression. No significant myelosuppression was observed at 10 and 15 mg/m2. Grade 3 myelosuppression was observed in two of six patients at 17.5 mg/m2. Responses included complete remission (CR) of pancreatic cancer (10 mg/m2), partial remission (PR) of malignant melanoma in two patients (20 mg/m2), and transient clinical and/or serologic improvement in five patients. The pharmacokinetics of L-PAM were not altered by WBH. Observed cytokine induction by WBH is also discussed in detail.. We conclude that L-PAM with 41.8 degrees C WBH is well tolerated. Clinical results are consistent with preclinical predictions and provide a foundation for second-generation trials now in progress.

Topics: Adult; Antineoplastic Agents, Alkylating; Biomarkers, Tumor; Combined Modality Therapy; Drug Administration Schedule; Female; Humans; Hyperthermia, Induced; Male; Melphalan; Middle Aged; Nausea; Neoplasms; Temperature; Vomiting

Resistance to alkylating agents and platinum compounds is associated with elevated levels of glutathione (GSH). Depletion of GSH by buthionine sulfoximine (BSO) restores the sensitivity of resistant tumors to melphalan in vitro and in vivo. In a phase I trial, each patient received two cycles as follows: BSO alone intravenously (i.v.) every 12 hours for six doses, and 1 week later the same BSO as cycle one with melphalan (L-PAM) 15 mg/m2 i.v. 1 hour after the fifth dose. BSO doses were escalated from 1.5 to 17 g/m2 in 41 patients.. The only toxicity attributable to BSO was grade I or II nausea/vomiting in 50% of patients. Dose-related neutropenia required an L-PAM dose reduction to 10 mg/m2 at BSO 7.5 g/m2. We measured GSH in peripheral mononuclear cells (PMN), and in tumor biopsies when available, at intervals following BSO dosing. In PMNs, GSH content decreased over 36 to 72 hours to reach a nadir on day 3; at the highest dose, recovery was delayed beyond day 7. The mean PMN GSH nadirs were approximately 10% of control at BSO doses > or = 7.5 g/m2; at 13 and 17 g/m2, all but two patients had nadir values in this range. GSH was depleted in sequential tumor biopsies to a variable extent, but with a similar time course. At BSO doses > or = 13 g/m2, tumor GSH was < or = 20% of starting values on day 3 in five of seven patients; recovery had not occurred by day 5. We measured plasma concentrations of R- and S-BSO by high-performance liquid chromatography (HPLC) in 22 patients throughout the dosing period. Total-body clearance (CLt) and volume of distribution at steady-state (Vss) for both isomers were dose-independent. The CLt of S-BSO was significantly less than that of R-BSO at all doses, but no significant differences in Vss were observed between the racemates. Harmonic mean half-lives were 1.39 hours and 1.89 hours for R-BSO and S-BSO, respectively.. A biochemically appropriate dose of BSO for use on this schedule is 13 g/m2, which will be used in phase II trials to be conducted in ovarian cancer and melanoma.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Buthionine Sulfoximine; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Female; Glutathione; Humans; Linear Models; Male; Melphalan; Methionine Sulfoximine; Middle Aged; Nausea; Neoplasm Recurrence, Local; Neoplasms; Neutropenia; Neutrophils; Radiography; Vomiting

In a Nordic multi-centre trial, 583 previously untreated multiple myeloma patients were randomized to receive melphalan-prednisone or melphalan-prednisone+ interferon alpha-2b at a dose of 5 million units subcutaneously, 3 d/week. A quality-of-life study was integrated into the trial, using the EORTC QLQ C-30 questionnaire supplemented with 11 questions concerning interferon toxicity. The questionnaire was completed prior to treatment and after 1, 6, 12, 24, 36 and 48 months. 90% of the patients participated in the quality-of-life study, and 83% completed all questionnaires submitted to them. During the first year of treatment the patients on interferon reported significantly more fever, chills, dry skin, fatigue, pain, nausea/vomiting and appetite loss than the control patients. There was a moderate reduction of the global quality-of-life score and slight, non-significant, reductions of physical, emotional, cognitive, social and role functioning scores. After the first year there were no statistically significant differences in any toxicity, symptom or quality-of-life score, except for an increased frequency of dizziness in the interferon group. As only 60% of the patients remained on interferon after 24 months, our data probably underestimate the potential toxicity of the drug. Although there was no significant survival benefit for the interferon patients, a 5-6 months prolongation of the response and plateau phase duration was observed. However, by intention-to-treat analysis, there was no late quality-of-life benefit for the interferon patients to compensate for the early impairment. Thus, the clinical significance of the plateau-phase prolongation is uncertain.

Topics: Activities of Daily Living; Aged; Antineoplastic Combined Chemotherapy Protocols; Fatigue; Feeding and Eating Disorders; Fever; Humans; Interferon alpha-2; Interferon-alpha; Melphalan; Multiple Myeloma; Nausea; Pain; Prednisone; Quality of Life; Recombinant Proteins; Social Behavior; Vomiting

The introduction of serotonin receptor (5-HT3) antagonists has improved the control of acute nausea and vomiting induced by cancer chemotherapy, but they seem to have little or no effect on delayed symptoms. Corticosteroids are known to reduce both acute and delayed nausea and vomiting. The aim of the present study was to test the hypothesis that a single high dose of dexamethasone (20 mg), a long-acting corticosteroid, given after cisplatin and in addition to ondansetron (8 mg three times a day), would enhance the control of both acute and delayed nausea and vomiting. A group of 104 chemotherapy-naive ovarian cancer patients, scheduled for at least three cycles of combination chemotherapy including cisplatin (50 mg/m2), were randomly allocated to receive either dexamethasone or placebo in addition to ondansetron. Two-thirds of the patients received doxorubin and melphalan on the day before cisplatin and 1/3 received doxorubicin immediately before cisplatin. Unexpectedly we found, in all three chemotherapy cycles, that patients receiving dexamethasone suffered from more delayed nausea and vomiting than patients receiving placebo. In patients with no acute nausea or vomiting, the boomerang effect of dexamethasone could be seen on the first day after chemotherapy. In a follow-up study on 5 patients not included in the randomized trial, dexamethasone induced a pronounced reduction in urinary cortisol excretion on the day after chemotherapy with a return to normal excretion on day 2. It is concluded that a single high dose of dexamethasone does not seem appropriate for controlling delayed nausea and vomiting.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dexamethasone; Doxorubicin; Drug Therapy, Combination; Female; Humans; Hydrocortisone; Melphalan; Nausea; Ondansetron; Ovarian Neoplasms; Vomiting

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Biperiden; Cisplatin; Dexamethasone; Doxorubicin; Drug Therapy, Combination; Female; Humans; Imidazoles; Lorazepam; Melphalan; Metoclopramide; Middle Aged; Ondansetron; Ovarian Neoplasms; Vomiting

Thirty-three patients with symptomatic Waldenström's macroglobulinemia have been treated with the M-2 protocol (BCNU, cyclophosphamide, vincristine, melphalan, and prednisone). Therapy was administered every 5 weeks for 2 years and every 10 weeks for an additional 1-3 years. Median clinical and laboratory parameters included age 70 years (range 52-87), performance status 1 (1-3), prior therapy 7, weight loss 12, symptomatic hyperviscosity 13, splenomegaly 22, lymphadenopathy 7, hemoglobin 9.6 g/dl (6.7-14.6), IgM paraprotein level 2000 mg% (340-11,600), and serum viscosity 2.1 (1.4-6.0). Responses were observed in 27 patients, of whom 21 were partial responses. Survival ranges from 1 to 120+ months with 58% of patients projected to be alive at 10 years. Twenty-one patients remain alive, of whom 10 are greater than or equal to 6 years from initiation of therapy with M-2. Treatment has been well tolerated with usually only mild to moderate hematologic toxicity. Median nadir white blood cells during the first cycle was 3000/mm3 (1000-5500). Peripheral neuropathy was seen in 54% secondary to vincristine. Nausea/vomiting, anemia requiring transfusions, and alopecia were each noted in approximately 25% of patients. Sepsis was observed in 2 patients. Two characteristics, age and prior therapy, were found to be of borderline statistical significance (p = 0.03) using univariate analysis but were not significant with multivariate analysis. The M-2 protocol may be able to produce prolonged survival in the majority of patients with Waldenström's macroglobulinemia. Additional trials are needed to develop recommendations for therapy as well as factors predictive for survival and suitability for treatment.

Topics: Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Drug Administration Schedule; Humans; Leukopenia; Melphalan; Nausea; Prednisone; Vincristine; Vomiting; Waldenstrom Macroglobulinemia

Topics: Bone Marrow; Breast Neoplasms; Clinical Trials as Topic; Drug Therapy, Combination; Female; Humans; Melphalan; Menopause; Methotrexate; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is common in patients with lymphoma and multiple myeloma (MM) receiving high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT). Despite a standard triple antiemetic regimen of a neurokinin-1 (NK1) receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone is recommended, how to control the protracted CINV in ASCT setting remains an intractable problem. Here, we retrospectively analyze CINV data of 100 patients who received either SEAM (semustine, etoposide, cytarabine, melphalan) or MEL140-200 (high-dose melphalan) before ASCT, evaluate the efficacy and safety of multiple-day administration of fosaprepitant combined with tropisetron and olanzapine (FTO), and compare the results to those of patients who received a standard regimen of aprepitant, tropisetron, and dexamethasone (ATD). The overall rate of complete response (CR), defined as no emesis and no rescue therapy, is 70% in the FTO group compared to 36% in the ATD group. Although CR rates are comparable in the acute phase between the two groups, significantly more patients treated by FTO achieve CR in the delayed phase than those treated by ATD (74% vs. 38%, p < 0.001). Moreover, FTO treatment significantly reduced the percentage of patients who are unable to eat, as well as the requirement for rescue medications. Both regimens are well tolerated and most adverse events (AEs) were generally mild and transient. In conclusion, the antiemetic strategy containing multiple-day administration of fosaprepitant is safe and effective for preventing CINV in lymphoma and MM patients, particularly in the delayed phase.

Topics: Antiemetics; Antineoplastic Agents; Dexamethasone; Hematopoietic Stem Cell Transplantation; Humans; Lymphoma; Melphalan; Morpholines; Multiple Myeloma; Nausea; Olanzapine; Retrospective Studies; Transplantation Conditioning; Transplantation, Autologous; Tropisetron; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is one of the most frequent adverse events compromising quality of life (QoL) in patients undergoing autologous stem cell transplantation (ASCT). However, CINV prophylaxis is still lacking uniformity for high-dose melphalan (HDM), which is used to condition patients with multiple myeloma (MM). Netupitant/palonosetron (NEPA) is administered with dexamethasone (DEXA) for CINV prevention in several chemotherapy regimens. Our study aims to assess the efficacy of NEPA, without DEXA, in preventing CINV in 106 adult patients with MM receiving HDM and ASCT. All patients had antiemetic prophylaxis with multiple doses of NEPA 1 h before the start of conditioning and after 72 h and 120 h. A complete response (CR) was observed in 99 (93%) patients at 120 h (overall phase). The percentage of patients with complete control was 93%. The CR rate during the acute phase was 94% (n = 100). During the delayed phase, the CR rate was 95% (n = 101). Grade 1 nausea and vomiting were experienced by 82% and 12% of the patients, respectively. Grade 2 nausea was reported in 18% and vomiting in 10% of patients. Our results showed, for the first time, that NEPA, without DEXA, was a well-tolerated and effective antiemetic option for MM patients receiving HDM followed by ASCT.

Topics: Antiemetics; Dexamethasone; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Multiple Myeloma; Nausea; Palonosetron; Pyridines; Quality of Life; Quinuclidines; Transplantation, Autologous; Vomiting

Topics: Adult; Aged; Antiemetics; Dexamethasone; Drug Therapy, Combination; Female; Hematopoietic Stem Cell Transplantation; Humans; Induction Chemotherapy; Male; Melphalan; Middle Aged; Multiple Myeloma; Nausea; Palonosetron; Prospective Studies; Pyridines; Transplantation Conditioning; Transplantation, Autologous; Vomiting

High-dose melphalan (HDM) followed by autologous hematopoietic cell transplantation (auto-HCT) remains the standard-of-care therapy for multiple myeloma (MM) even with the availability of proteasome inhibitors and immunomodulatory drugs. Gastrointestinal (GI) toxicity is the main cause of morbidity after HDM. Amifostine, a cytoprotective agent, may reduce HDM-associated GI toxicity. We conducted a case control study comparing HDM + auto-HCT with or without amifostine for MM patients. One hundred and seven patients treated at University Hospitals Cleveland Medical Center who received pre-transplant amifostine were compared to 114 patients treated at MD Anderson Cancer Center without use of this agent. Amifostine 740 mg/m

Topics: Adult; Aged; Amifostine; Case-Control Studies; Combined Modality Therapy; Diarrhea; Disease-Free Survival; Female; Gastrointestinal Diseases; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Nausea; Transplantation, Autologous; Vomiting

Topics: Antineoplastic Agents; Aprepitant; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Nausea; Olanzapine; Retrospective Studies; Transplantation, Autologous; Vomiting

Acute and delayed chemotherapy-induced nausea and vomiting (CINV) occurs in most patients who receive high-dose melphalan and significantly affects patients' quality of life during autologous stem cell transplantation. Faced with unsatisfactory results using an aprepitant-based regimen, an olanzapine-based regimen was initiated, with the hope of improving the incidence of acute and delayed CINV. A retrospective study was conducted to compare the effectiveness of olanzapine- versus aprepitant-based regimens for CINV prevention in adult hematopoietic stem cell recipients who received high-dose melphalan.. We compared olanzapine (n = 43) to aprepitant (n = 54) and fosaprepitant (n = 20). Olanzapine was given orally at 5 mg twice daily for 5 days, aprepitant was given at 125 mg on day -1 and 80 mg on days 0 and 1, and fosaprepitant was given at 150 mg on day -1. The dose of 2 concomitant drugs (dexamethasone and 5-hydroxytryptamine type 3 receptor antagonist) was similar in the 2 groups. Nausea prevention was the primary endpoint. A complete response using a composite index of no emesis and no use of rescue medications was the secondary endpoint.. The results showed that olanzapine significantly reduced the number of patients who experienced acute (P < .0001) or delayed (P < .004) nausea and significantly reduced the use of rescue medications for acute-onset (P < .0046) and delayed-onset (P < .0001) CINV compared with aprepitant.. Compared with fosaprepitant, olanzapine reduced the number of patients with acute (P < .0318) and delayed (P < .1519) nausea and reduced the need for rescue medications for acute-onset (P < .0643) and delayed-onset (P < .0024) CINV.

Topics: Adult; Aged; Algorithms; Antiemetics; Aprepitant; Benzodiazepines; Disease Management; Female; Hematopoietic Stem Cell Transplantation; Humans; Induction Chemotherapy; Male; Melphalan; Middle Aged; Morpholines; Multiple Myeloma; Myeloablative Agonists; Nausea; Olanzapine; Transplantation Conditioning; Treatment Outcome; Vomiting

To assess the impact of single-dose fosaprepitant on nausea and emesis after BEAM and high-dose melphalan conditioning regimens for autologous hematopoietic stem cell transplantation.. In a single-center cohort study patients receiving melphalan containing hematopoietic stem cell transplantation regimens who received a one-time dose of 150 mg IV fosaprepitant (n = 56) were compared to a historical control (n = 70).. The primary endpoint of no emesis from melphalan administration through five days afterward was 80% for the fosaprepitant group versus 66% in the control group (p = 0.068). Addition of fosaprepitant demonstrated significant improvement in emetic episodes per patient during the entire assessment period (p = 0.011) and days 1-5 after melphalan (p = 0.045). Fosaprepitant resulted in no substantial nausea during the entire assessment period in 37% of high-dose melphalan patients and 57% of BEAM patients.. Further studies are suggested to investigate the optimal number and timing of doses of fosaprepitant in this setting.

Topics: Aged; Antiemetics; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cohort Studies; Cytarabine; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Morpholines; Nausea; Podophyllotoxin; Prospective Studies; Retrospective Studies; Transplantation Conditioning; Vomiting

High-dose melphalan has been gaining recognition as a highly emetogenic agent used in hematopoietic stem cell transplantation (HSCT). The aim of this retrospective study was to elucidate the efficacy of aprepitant in preventing high-dose melphalan-induced emesis. Sixty patients who received melphalan (70 mg/m(2)/day, 2 days) and fludarabine (125 mg/m(2)/day, 5 days) as conditioning for allogeneic HSCT for hematological malignancies, and who received ondansetron and methylprednisolone as an antiemetic prophylaxis, were eligible. Twenty of these 60 patients also received aprepitant for 5 days (aprepitant group); the remaining 40 patients served as a control. The rates of complete response (CR), defined as no emesis without rescue medications, and complete protection (CP), defined as no emesis with or without rescue medications, were assessed between the two groups. The observation period was 12 days from the first day of melphalan administration. The CR and CP rates were significantly higher in the aprepitant group than in the control group during the observation period (35 % versus 10 %, P < 0.05; 85 % versus 33 %, P < 0.001; respectively). These results suggest that aprepitant in combination with ondansetron and steroid effectively ameliorates nausea and vomiting caused by the high-dose melphalan-based conditioning for allogeneic HSCT.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Morpholines; Myeloablative Agonists; Nausea; Retrospective Studies; Transplantation Conditioning; Transplantation, Homologous; Vomiting

In an attempt to limit toxicities associated with dose-intensive therapy used for transplant regimens, we performed a pilot study using amifostine with high-dose busulfan (12 mg/kg), melphalan (100 mg/m2), and thiotepa (500 mg/m2) in 21 patients with a variety of malignancies. After 3 days of oral busulfan, amifostine was given at 910 mg/m2 IV for 10 minutes, preceding the infusion of each of 2 doses of melphalan and thiotepa given for 4 days. Antiemetic premedication for amifostine was given to all patients. The median patient age was 50 years (range: 32-65 years). Twenty-one patients received 82 separate amifostine infusions. One patient discontinued amifostine after the second dose because of severe nausea and emesis, and two infusions were temporarily held secondary to hypotension. Of these 82 cycles, there was a total of 37 episodes of nausea/vomiting, 28 episodes of sneezing, 11 episodes of flushing, and 1 episode of oral paresthesia. Systolic blood pressure and mean arterial pressure decreased by a mean of 8.4 mm Hg and 5.0 mm Hg, respectively. In general, the infusion was well tolerated. Patients were observed until discharge home (N = 15), until initiation of an additional tandem transplant procedure (N = 4), or until death (N = 2). All twenty-one patients experienced nonhematologic toxicities grade II or greater. Grade II toxicities included mucositis (N = 21), gastrointestinal (N = 3), skin (N = 1), and liver (N = 1), and grade III toxicities included liver (N = 1). Mucositis was also scored according to a detailed toxicity assessment. Mucositis did not appear to be improved with amifostine when compared with a control group of patients not receiving amifostine. Renal dysfunction after transplantation was decreased in the amifostine group, whereas there was no significant effect on posttransplant hepatic dysfunction. Although these data demonstrate the feasibility of delivering parenteral amifostine in conjunction with dose-intensive chemotherapy and autologous peripheral blood stem cell transplantation, there was no evidence of a significant reduction in nonmarrow toxicities.

Topics: Adult; Aged; Amifostine; Antiemetics; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Blood Pressure; Busulfan; Feasibility Studies; Female; Flushing; Hematopoietic Stem Cell Transplantation; Humans; Hypotension; Male; Melphalan; Middle Aged; Mucous Membrane; Neoplasms; Pilot Projects; Protective Agents; Sneezing; Thiotepa; Transplantation, Autologous; Vomiting

A total of 33 patients with myeloma receiving treatment with high-dose melphalan (140-200 mg/m2 i.v.) were given the 5HT3 antagonist Ondansetron (Glaxo) as an antiemetic. In 42% of patients, emetic episodes were either abolished (15%) or reduced to two or less (27%). Efficacy was not related to scheduling (two regimens) or total dose. No sedative or other significant side effects were seen. Ondansetron is a highly effective non-sedative antiemetic that justifies further assessment in combination with other antiemetics in patients receiving cytotoxic drugs associated with the production of severe nausea and vomiting.

Topics: Administration, Oral; Antiemetics; Drug Administration Schedule; Drug Evaluation; Female; Humans; Imidazoles; Infusions, Intravenous; Male; Melphalan; Middle Aged; Multiple Myeloma; Nausea; Ondansetron; Serotonin Antagonists; Vomiting

From January 1978 to October 1982, 47 patients with histological diagnosis of epithelial cancer of the ovary received peptichemio (PTC) at a dose of 70 mg/m2 (maximum, 120 mg total) every 15 days. Forty-two patients are now evaluable: 27 with stage III and 15 with stage IV disease. All patients but four with stage IV disease had been pretreated and had received at least one drug combination (median, three drugs per patient, including alkylating agents). Before the administration of PTC, the tumor extension in the abdomen was carefully assessed in all patients: ten patients had residual tumor less than 2 cm in diameter, while 32 patients had tumor greater than 2 cm in diameter. Objective responses were obtained in ten patients (23.8%): six complete remissions and one partial remission were observed in stage III patients and one complete remission and two partial remissions were observed in stage IV patients. Of the ten responding patients, eight had tumors less than 2 cm in diameter before receiving PTC. The median duration of response was 16 months. The most frequent side effects were myelosuppression and phlebosclerosis. Bone marrow depression was a common finding after the third course in heavily pretreated patients. Accordingly, in these patients a schedule interval of 3 weeks should be more appropriate. Since most of the responders were in the "small tumor" category, PTC appears to be an active drug in patients with ovarian cancer having small tumors (less than 2 cm). On the other hand, the response rate in a nonselected population of patients remains to be clearly defined with further studies.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carcinoma; Drug Eruptions; Female; Humans; Leukocyte Count; Melphalan; Middle Aged; Nausea; Ovarian Neoplasms; Peptichemio; Platelet Count; Vomiting

Seventeen patients were treated with high-dose melphalan with autologous bone marrow transplant (ABMT) and cyclophosphamide pretreatment. All of the patients had marrow reconstitution. Although there was one death caused by infection, high-dose melphalan with ABMT causes toxicity that is generally acceptable, and can achieve a high-response rate, but with responses of short duration in tumors resistant to standard-dose combination chemotherapy. In other poor-prognosis tumors that are sensitive to chemotherapy, or can be debulked surgically, or locally irradiated, high-dose melphalan with ABMT given as late intensification therapy may significantly prolong time to relapse, and ultimately prolong survival.

Topics: Adult; Bacterial Infections; Bone Marrow Transplantation; Combined Modality Therapy; Cyclophosphamide; Female; Humans; Male; Melphalan; Middle Aged; Myeloproliferative Disorders; Neoplasms; Prognosis; Vomiting

Asaley is an L-leucine derivative of sarcolysin which is more active against some rodent tumors. Studies in the USSR demonstrated activity in patients with ovarian and breast carcinoma, Hodgkin's disease, and multiple myeloma. This study in 73 evaluable patients indicated that an appropriate oral dose for patients with adequate bone marrow is 800 mg/M2/day X 4 days at 5-6 week intervals. The most common toxicities were myelosuppression, nausea, and vomiting. Antitumor activity was observed in 2 of 24 evaluable patients with melanoma, and stabilization of previously progressive disease was observed in patients with adenocarcinoma of the colon, multiple myeloma, lymphoma, breast carcinoma, and thyroid carcinoma. Responses were minimal and of short duration but most of the patients had received extensive prior therapy.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Animals; Bone Marrow; Colonic Neoplasms; Drug Administration Schedule; Drug Evaluation; Female; Humans; Male; Melanoma; Melphalan; Middle Aged; Multiple Myeloma; Nausea; Neoplasm Metastasis; Neoplasms; Rats; Remission, Spontaneous; Vomiting

Topics: Adolescent; Adult; Antibiotics, Antineoplastic; Carcinoma, Squamous Cell; Chlorpromazine; Cyclophosphamide; Female; Fever; Humans; Liver Neoplasms; Lymphatic Metastasis; Lymphoma, Large B-Cell, Diffuse; Male; Mechlorethamine; Melphalan; Middle Aged; Nasopharyngeal Neoplasms; Nausea; Neoplasm Recurrence, Local; Olivomycins; Thiotepa; Thrombocytopenia; Tonsillar Neoplasms; Vomiting

Topics: Adolescent; Adult; Alopecia; Bone Marrow Diseases; Bone Neoplasms; Cyclophosphamide; Female; Humans; Male; Melphalan; Sarcoma, Ewing; Vomiting