Biomedical subjects

D Bafaloukos

Publications and source records attributed to D Bafaloukos.

At least 55 records · Page 3Linked to original sources

PubMed1999

Carboplatin, methotrexate and 5-fluorouracil in combination with medroxyprogesterone acetate (JMF-M) in the treatment of advanced or recurrent endometrial carcinoma: A Hellenic cooperative oncology group study.

Twenty-three patients with advanced or recurrent endometrial carcinoma entered a prospective study of chemotherapy which consisted of carboplatin (300 mg/m2), methotrexate (30 mg/m2), and 5-fluoruracil (500 mg/m2) given on day 1, in a 3-weekly schedule, in combination with medroxyprogesterone acetate (MPA): 300 mg daily, p. o., until progression (JMF-M regimen). None had received prior chemotherapy and/or hormonotherapy for metastatic disease. Ten patients had received radiotherapy. Response to treatment was evaluated every two courses. Objective response was seen in 17 of the 23 patients (74%, 95% confidence interval = 52-90%), with 2 long-lasting complete responses (9%). The median response duration was 10+ months (3-45+). The median survival was 16+ months (2-45+). The 2 complete responders, the first in the lung and the second in groin nodes, are without evidence or recurrence after 32 and 45 months, respectively. The regimen was given on an outpatient basis and was well tolerated. The major toxic effects were myelosuppression (less than 14% leukopenia, anemia and thrombocytopenia). The MPA-related side effects were: weight gain (22%), hypertension (17%) and thromboplebitis (17%). In 2 patients, consolidation treatment with MPA was discontinued because of thromboplebitis. In conclusion, the JMF-M regimen is highly active with an acceptable toxicity in patients with recurrent or metastatic endometrial carcinoma.

Adult↗

PubMed1998

First-line chemotherapy with paclitaxel by three-hour infusion and carboplatin in advanced breast cancer (final report): a phase II study conducted by the Hellenic Cooperative Oncology Group.

PURPOSE: To evaluate the activity and toxicity of the combination of paclitaxel given by three-hour infusion, and carboplatin as first-line chemotherapy in patients with advanced breast cancer (ABC). BACKGROUND: Paclitaxel is an active agent in ABC. Furthermore, our group has shown that the combination of paclitaxel and carboplatin is effective in anthracycline-resistant ABC. PATIENTS AND METHODS: From January 1996 until March 1997, 66 women with ABC were treated with paclitaxel (175 mg/m2) by three-hour infusion followed by carboplatin at an AUC of 6 mg x min/ml every three weeks. The median age of the patients was 56 years (range 28-75). A total of 39 patients had received adjuvant chemotherapy and 22 of them were treated with an anthracycline or mitoxantrone-containing regimen. RESULTS: A total of 324 cycles (median: six) were administered, 273 (85%) of them at full dose. The median number of delivered cycles was six. The median delivered dose intensity (DI) of paclitaxel was 55.1 mg/m2/week (range 30.5-69.3) and the relative DI was 0.95 (range 0.5-1.2). Eight patients (12%, 95% confidence interval (CI): 5%-22%) achieved complete and 28 (42%, 95% CI: 30%-55%) partial responses. Grade 3-4 toxicities included anemia (5%), granulocytopenia (24%), thrombocytopenia, nausea/vomiting and allergic reaction (3% each), myalgias/arthralgias and neurotoxicity (1.5% each). Febrile neutropenia occurred in eight (12%) patients. Alopecia was universal. After a median follow-up of 17.3 (range 0.07-24.5) months, 48 (72%) patients have demonstrated tumor progression and 24 (36%) have died. Median time to progression was 8.6 (range 0.07-23+) months and median survival 20.4 (range 0.07-24.5+) months. CONCLUSIONS: The combination of paclitaxel and carboplatin has moderate activity in ABC and can be easily delivered on an outpatient basis with manageable toxicity. This regimen may be useful especially in patients to whom anthracyclines or cisplatin administration is precluded because of other concomitant diseases.

Adult↗

PubMed1998

Paclitaxel and carboplatin as first-line chemotherapy for advanced breast cancer.

In a phase II study, 66 patients with advanced breast cancer (median age 56 years; range, 28 to 75 years) were treated with paclitaxel (Taxol), 175 mg/m2 infused over 3 hours, and carboplatin (Paraplatin), dosed to attain an area under the concentration-time curve (AUC) of 6 mg x min/mL; treatment was repeated every 3 weeks. A total of 38 (58%) patients had received prior adjuvant chemotherapy, 21 with a regimen containing an anthracycline or mitoxantrone (Novantrone). As of May 1997, 295 cycles of paclitaxel-carboplatin have been administered, 248 (84%) at full dose. The relative dose intensity of paclitaxel is 0.9 (range, 0.5 to 1.2). Of the 66 patients, 8 (12%) have achieved a complete response and 27 (41%) a partial response, for a total response rate of 53%. Grade 3 to 4 toxicities have included anemia (5%), leukopenia (25%), thrombocytopenia (5%), nausea/vomiting (7%), myalgias/arthralgias (4%), allergic reaction, neurotoxicity, and infection (2% each). Alopecia has been universal. Median time to progression is 8.9 months; median survival has not yet been reached. We conclude that the combination of paclitaxel and carboplatin has significant activity in advanced breast cancer and can easily be administered on an outpatient basis with manageable toxicity.

Adult↗

PubMed1997

Baldness and other correlates of sex hormones in relation to testicular cancer.

There is evidence that sex hormones and intrauterine factors are involved in the etiology of testicular cancer. We evaluated the importance of perinatal and adult life correlates of sex hormones as risk factors for testicular cancer in a case control study of 97 incident, histologically confirmed cases, residents of the Greater Athens area and environs, who were diagnosed in the 3 specialized cancer hospitals and the major General Hospital in Athens during the 2 year period 1993-94. Cases were age-matched to 2 healthy controls from the same study base. Both cases and controls as well as their mothers were interviewed by the same investigator and the data were analyzed through conditional logistic regression. The odds ratio for testicular cancer was elevated among persons born after a pregnancy characterized by severe nausea. Among the adult life factors, higher body mass was associated with reduced risk, as was evidence of baldness. To the extent that nausea during pregnancy reflects higher levels of pregnancy estrogens on the one hand, and baldness is linked to androgens on the other, our data suggest that estrogens in the intrauterine life and androgens at later stages may have sequential opposing effects for the development of testicular cancer.

Adult↗

PubMed1997

A phase II study of paclitaxel in platinum pretreated ovarian cancer. A Hellenic Cooperative Oncology Group study.

Paclitaxel was administered at a dose of 175 mg/m2 in a 3-hour infusion every 3 weeks in platinum pretreated patients with ovarian cancer. 51 patients with a median age of 57 years entered the study. 33 (65%) presented with stage III and 18 (35%) with stage IV disease. 39 patients (76%) were previously treated with only one and 12 (24%) with two regimens. The median interval from the last previous chemotherapy was 4 months (range, 1-65). Ninety-eight per cent of the planned dose of paclitaxel was actually delivered. Overall and complete response rate was 26% (13/51) and 16% (8/51), respectively. All complete responses were observed among patients previously treated with only one regimen. Median time to progression was 10.26 months (range, 4.9-25.2+) and median survival 15.6 months (range, 1.3-27.1+). Factors influencing survival were performance status and the number of previous regimens.

Adult↗

PubMed1997

Paclitaxel by 3-h infusion and carboplatin in anthracycline-resistant advanced breast cancer. A phase II study conducted by the Hellenic Cooperative Oncology Group.

37 patients with advanced breast cancer resistant to anthracyclines were treated with paclitaxel 200 mg/m2 by 3-h infusion and carboplatin at an area under the curve of 7 mg.min/ml every 4 weeks with G-CSF support. There were 5 (14%, 95% CI 3-25%) complete and 11 (30%, 95% CI 15-45%) partial responders. Median duration of response was 11.5 months (range 5.2-16.8+), median time to progression 8 months (range 0.26-16.8+) and median survival 12 months (range 0.5-19.6+). Grade 3-4 leucopenia (27%), thrombocytopenia (10%) and diarrhoea (5%) were noted. In conclusion, the combination of paclitaxel and carboplatin is active and well tolerated in patients with advanced breast cancer resistant to anthracyclines.

Adolescent↗

PubMed1997

A randomized study of epirubicin monotherapy every four or every two weeks in advanced breast cancer. A Hellenic Cooperative Oncology Group study.

PURPOSE: To evaluate the impact on the response rate in patients with advanced breast cancer (ABC) of the doubling of the dose intensity (DI) of epirubicin monotherapy. PATIENTS AND METHODS: From January 1991 until April 1996, 167 patients with ABC were randomized to receive epirubicin (110 mg/m2) either every four (81 patients, group A) or every two weeks (86 patients, group B). Filgrastim (5 micrograms/kg/daily) was administered prophylactically on days 2-12 of each cycle. RESULTS: The two groups were equally balanced in terms of major patient and tumor characteristics. Even though the median cumulative dose of epirubicin was identical in the two groups (651 mg/m2), the median DI of epirubicin was doubled in group B (27.2 vs. 52.9 mg/m2/wk, respectively). The complete response (CR) rate was significantly increased in group B (5%, 95% CI: 0.16%-9.84% vs. 17%, 95% CI: 8.9%-25.08%, P = 0.011), although overall response rates were similar (49% vs. 53%, P = 0.5957). Also, there was no significant difference in the incidence of grade 3-4 toxicity between the two groups. After a median follow-up of 25 months (range, 0.43-43.3+) no significant difference was observed in the duration of response (median, 10 months vs. 8.5 months, P = 0.5130), time to progression (median, 7.2 months vs. 7.4 months, P = 0.2970) or survival (median, 14.6 months vs. 14.9 months, P = 0.4483). Logistic regression analysis showed that performance status was a significant variable for response (P = 0.0068) and multivariate analysis using the Cox proportional hazards model revealed that performance status was significant for survival (P = 0.0049), while the presence of multiple metastases (P = 0.0020) was significant for time to progression. CONCLUSION: Doubling the planned DI of epirubicin monotherapy significantly increases the CR rate but has no influence on time to progression or survival in patients with ABC.

Adult↗

PubMed1997

Paclitaxel with carboplatin versus paclitaxel with carboplatin alternating with cisplatin as first-line chemotherapy in advanced epithelial ovarian cancer: preliminary results of a Hellenic Cooperative Oncology Group study.

Ninety previously untreated patients with advanced epithelial ovarian cancer (International Federation of Gynecology and Obstetrics stages IIC, III, and IV) were randomized, after initial cytoreductive surgery, to receive paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 as a 3-hour infusion with either carboplatin at an area under the concentration-time curve of 7 (group A) or carboplatin at an area under the concentration-time curve of 7 on courses 1, 3, and 5, alternating with cisplatin 75 mg/m2 on courses 2, 4, and 6 (group B). Treatment was given every 3 weeks, up to a total of six courses. Sixty-one patients (33 and 28 patients in groups A and B, respectively) had residual disease after the initial cytoreductive surgery. Patients with measurable or evaluable disease had a high overall response (82% v 57%). A 52% and 39% complete response rate for groups A and B, respectively, with no statistically significant difference between the groups was also observed. With a median follow-up of 12 months (range, 0.33 to 24 months), 29 patients have progressed (18 and 11 in groups A and B, respectively), and 13 have died (seven and six, respectively). Median time to progression was 20.36 months (range, 0.20 to 23.54 months) for group A, whereas this has not yet been reached for group B. Median survival has not yet been reached, but there is no significant difference between the two groups (P = .6972). Treatment was generally well tolerated. Grade 3 and 4 neutropenia was 20% and 32% for groups A and B, respectively, while grade 3 and 4 thrombocytopenia was 4% and 7%, respectively, with no significant difference between the two groups. In conclusion, both combinations seem very active for the treatment of advanced epithelial ovarian cancer and are associated with acceptable toxicity.

Adult↗

PubMed1996

A phase II study of paclitaxel in advanced breast cancer resistant to anthracyclines.

33 women with advanced breast cancer resistant to anthracyclines were treated with paclitaxel 175 mg/m2 in a 3 h infusion every 3 weeks. The median age was 53 years (range 30-72) and the median performance status was 1 (range 0-2). 24 (73%) patients had visceral metastases while 22 (67%) had > or = two involved sites. 23 (70%) patients received anthracycline or mitoxantrone in an adjuvant setting and 21 (64%) for advanced disease. There were two (6%, 95% confidence interval (CI) 1-20%) complete responses (CRs) and 12 (36%, 95% CI 20-55%) partial responses (PRs). Median dose intensity of paclitaxel delivered was 58 mg/m2/week. Median time to progression was 24 weeks (range 4-61) and median survival was 41 weeks (range 8-66). Grade 3-4 toxicities included leucopenia (9%), stomatitis (3%), alopecia (91%), neurotoxicity (9%), infection (3%) and diarrhoea (3%). In conclusion, paclitaxel at a dose of 175 mg/m2 exhibits significant activity in advanced breast cancer resistant to anthracyclines.

Adult↗

PubMed1996

Recombinant interferon ALFA-2A in combination with carboplatin, vinblastine, and bleomycin in the treatment of advanced malignant melanoma.

Thirty-four patients with advanced malignant melanoma were treated with recombinant alpha-interferon (IFN) and chemotherapy consisting of carboplatin, vinblastine, and bleomycin (CVB). CVB was given for four cycles and IFN for 1 year or until progression. Of the 34 analyzed patients, 17 (50%) achieved an objective response, including two complete (6%) and 15 partial responses (44%). Responses were noted in cutaneous, lymph node, and pulmonary sites, with a median time to disease progression of 5 months (range, 3-20 months). The median survival from onset of therapy was 8 months (range, 1-22 months) for the 34 patients. Ninety-four percent of the patients experienced flu-like symptoms and 82% fatigue or weakness. Leukopenia grade 3-4 was observed in four patients (12%). There were two toxicity-related deaths (6%); one from bleomycin-induced pneumonitis and one from neutropenic sepsis. It is concluded that the addition of IFN to CVB regimen, in this study, showed no apparent advantage on response rates, disease-free interval, or survival. The observed treatment-related mortality was unacceptably high. IFN administered as maintenance therapy following CVB conferred no survival benefit.

Adult↗

PubMed1995

High-dose epirubicin and r-met-hu G-CSF (filgrastim) in the treatment of patients with advanced breast cancer: A Hellenic Cooperative Oncology Group study.

The delivery of high-dose epirubicin in patients with advanced breast cancer usually entails serious myelotoxicity and frequent treatment delays. Concurrent administration of G-CSF probably allows the administration of epirubicin on schedule with minimal morbidity. From August 1990 to February 1992, 42 women with advanced breast cancer were treated with six cycles of epirubicin 110 mg/m2 every 4 weeks. Filgrastim 5 micrograms/kg per day for 14 days was administered subcutaneously starting 24 hours after chemotherapy. All patients had multiple metastatic sites, and 39 had visceral metastases. All cases were evaluable for response, toxicity, and survival. Treatment was delayed in only two cases. The actually administered average dose per unit time per patient amounted to 99.6% of the dose prescribed by the protocol. Two (4.5%; 95% confidence interval [C.I.] 0-16%) patients demonstrated a complete response and 14 (33%; 95% C.I. 19-49%) a partial response. Median time to progression was 31 weeks and median survival was 60 weeks. Severe granulocytopenia was seen in six patients; stomatitis and diarrhea in one patient each. Myoskeletal pain was noticed in 23 (55%) patients, while cardiac problems were reported in 3 cases. The present study shows that the prophylactic use of r-met-hu G-CSF allows the administration of high-dose epirubicin every 4 weeks with minimal morbidity and an improved quality of life.

Adult↗

PubMed1994

Evaluation of six tumor markers in patients with carcinoma of unknown primary.

We have retrospectively evaluated six serum tumor markers in 85 patients with carcinoma of unknown primary. The serum levels of carcinoembryonic antigen (CEA), CA 19-9, CA 15-3, CA 125, beta-chorionic gonadotropin (beta-HCG) and alpha-fetoprotein (AFP) were related with the histological pattern (undifferentiated carcinoma or adenocarcinoma), the number and the site of metastases, as well as the response to chemotherapy and the patients' survival. More than 40% of the patients had increased serum levels of all six tumor markers, except of AFP which was found to be increased in only 17% of them. Increased levels of CA 19-9 were related to metastatic adenocarcinoma, whereas CA 19-9 and CA 15-3 had a relationship with more advanced disease. Patients with liver involvement had higher mean levels of CEA and CA 19-9 as compared to those with nodal disease. None of these markers was found to have a predictive value for response to chemotherapy or survival. Although the present study has a retrospective nature, it allows us to conclude that patients with CUP have a nonspecific over-expression of the above serum tumor markers and that routine use of these markers does not offer any diagnostic or prognostic assistance.

Adenocarcinoma↗

PubMed1994

Intensive chemotherapy with high-dose epirubicin every 2 weeks and prophylactic administration of filgrastim in advanced breast cancer.

50 women with advanced breast cancer were treated with an intensified regimen which consisted of high-dose epirubicin (110 mg/m2) every 2 weeks and filgrastim (5 micrograms/kg) subcutaneously for 13 days, starting 24 h after chemotherapy. 44 patients completed all six cycles. The median interval between cycles of treatment was 14.3 days. The actually administered median dose per unit time per patient was 53 mg/m2/week, amounting to 97.2% of the dose prescribed by the protocol. 7 [14%, 95% confidence interval (C.I.) 4-24%] patients achieved a complete and 25 (50%, 95% C.I. 36-64%) a partial response. Median time to progression was 32 weeks and median survival 64 weeks. Stomatitis and fever each occurred in 7 (14%) patients. Grade 3 haematological toxicity was observed in 6 (12%) patients. 1 (2%) patient developed grade 4 cardiac toxicity. This intensified regimen appears to be a well tolerated and effective treatment in advanced breast cancer.

Adult↗

PubMed1994

Adjuvant chemotherapy with dacarbazine, vindesine, and cisplatin in pathological stage II malignant melanoma.

Following curative lymph node dissection, 28 patients with pathological Stage II malignant melanoma (metastatic to regional lymph nodes) received adjuvant chemotherapy with dacarbazine, vindesine, and cisplatin (DVP); 32 more patients with similar characteristics refused adjuvant treatment. In the treated group, 15 patients (53%) developed dissemination of disease after 4 to 29 months; 20 (62%) of the patients who refused adjuvant treatment recurred after 4 to 25 months and received palliative treatment with DVP. No significant differences in survival or disease-free survival according to different patient characteristics could be detected between these two groups with the available patient population. Large and well-designed prospective randomized trials are required to determine if the adjuvant use of this treatment schedule, which includes the three most active drugs improves survival in patients with nondisseminated melanoma.

Adult↗

PubMed1993

First-line combination chemotherapy with mitoxantrone, methotrexate, vincristine and carboplatin (MIMOC) in advanced breast cancer.

51 patients with stage IIIB and IV breast cancer entered a prospective phase II study of combination chemotherapy that consisted of mitoxantrone (8 mg/m2) day 1, methotrexate (25 mg/m2) day 1, vincristine (1 mg/m2) day 2 and carboplatin (250 mg/m2) day 2 (MIMOC) given in a 3-weekly schedule. None had received prior chemotherapy for metastatic disease, although 16 patients were given adjuvant chemotherapy. Objective response to treatment was seen in 29 of 48 patients analysed for response (60%) with 8 complete responses (CR). 7 out of 8 patients with stage IIIB disease responded, 2 of them completely. Responses were seen in all sites but the best results were achieved in lung metastases with 50% CR. The median duration of response was 8 months and the median time to disease progression was 12 months. The main toxicity was nausea and vomiting which was severe in 20% of the patients. Other toxicities were mild. MIMOC was administered on an out-patient basis and appears to be effective as first-line treatment in advanced breast cancer.

Adult↗

PubMed1992

Antiproliferative activity of vinorelbine (Navelbine) against six human melanoma cell lines.

We compared in vitro the cytotoxic activity of vinorelbine (VRB) (Navelbine, 5'-nor-anhydro-vinblastine) a novel Vinca alkaloid, with that of vinblastine (VBL) vincristine (VCR) and vindesine (VDS). Five continuous human melanoma cell lines (C32, G361, StMl11a, StMl12d and StMl14a) and a new line WHMel 1, were used in this study. In growth-inhibition assays, VDS and VRB exhibited comparable cytotoxicity against the C32 and G361 melanoma lines; the effect being dose- and time-dependent. VRB appeared less inhibitory compared to VDS in the lowest concentrations (0.1-1 nM). The same activity was observed with 0.1-1 microM. These drugs exhibited comparable growth inhibition at clinically achievable doses. The MTT assay was used to compare VBL, VCR, VDS, and VRB. Overall IC50 values (concentration required to reduce viability by 50%) ranged from 1 pM to 10 nM. The reduction in cell viability with VRB was similar to that observed with the reference drugs in four out of five lines tested by this method. However a trend was observed for IC50 values to be lower with VBL and VDS. In clonogenic assays (StMl11a, StMl12d and StMl14a lines, 1 h exposure) VRB and VDS produced the same reduction in survival. Survival curves were exponential followed by a terminal plateau. IC50 values ranged from 60 nM to 70 nM. Our results indicate that VRB has in vitro activity against six melanoma lines with differing phenotypic characteristics.

Antineoplastic Agents↗

PubMed1992

Subsets of tumors responsive to cisplatin or carboplatin combinations in patients with carcinoma of unknown primary site. A Hellenic Cooperative Oncology Group Study.

In this retrospective analysis 48 patients with metastatic undifferentiated carcinoma, adenocarcinoma and epidermoid carcinoma of unknown origin were studied. The purpose of this analysis was to evaluate both the response rate and the toxicity of combination chemotherapy containing cisplatin or carboplatin, and to attempt to identify certain clinical subsets of patients sensitive to these drugs. Four patients were not evaluable and 13 (29.5%), eight of the 34 treated with regimens containing cisplatin and 5/14 with carboplatin-based chemotherapy, responded to treatment. Six of the 23 with undifferentiated tumours, 4/17 with adenocarcinomas and 3/8 with epidermoid cancers responded to chemotherapy. Four of 6 women with adenocarcinoma of the peritoneal cavity, 5/11 with undifferentiated carcinomas with midline distribution and 3/5 with epidermoid carcinomas of the cervical nodes responded. Seven patients achieved complete and six partial remissions. The mean duration of response was nine months; a number of patients enjoyed prolonged and/or durable remissions. Toxicity was tolerable. We conclude that: (a) both cisplatin and carboplatin are active agents in this syndrome with one-third of the evaluable patients responding, and (b) there may be chemosensitive subgroups, such as patients with peritoneal adenocarcinomatosis, undifferentiated carcinoma with midline distribution and metastatic epidermoid carcinoma of the neck nodes. The effectiveness of carboplatin in these patients and the responsiveness of metastatic epidermoid carcinoma of unknown origin have not been adequately dealt with in the literature.

Adenocarcinoma↗

PubMed1992

The prognostic significance of immune changes in patients with renal cell carcinoma treated with interferon alfa-2b.

PURPOSE: To evaluate the response rate and the immunorestorative properties of subcutaneously administered interferon alfa-2b (IFN-A2b) in patients with advanced renal cell carcinoma (RCC) and to correlate the immune status with the clinical responses. PATIENTS AND METHODS: Twenty-six patients with advanced RCC were treated with recombinant IFN-A2b. The dose was increased progressively from 5 x 10(6) IU the first week to 10 x 10(6) IU the second week, and thereafter to 15 x 10(6) IU subcutaneously. RESULTS: Four patients (15%) achieved partial responses (PRs), and five patients (19%) had stable disease (S), whereas 17 patients (65%) progressed. In all patients, blood was withdrawn before IFN treatment and monthly thereafter. T lymphocytes after isolation from peripheral blood were tested for proliferation in the autologous mixed lymphocyte reaction (autoMLR) and allogeneic mixed lymphocyte reaction (alloMLR), interleukin-2 (IL-2) production, expression of IL-2 receptors during the alloMLR, and the production of interleukin-1 (IL-1) by peripheral-blood monocytes. Twelve patients were assessable, four patients had a PR, one patient had S, and seven patients had progressive disease. Striking increases were demonstrated in all parameters 1 month after treatment with IFN-A2b in the four patients who responded and the patient with S. Namely, the autoMLR responses showed a mean increase of 250%, the IL-2 production 247%, the expression of IL-2-specific receptors 446%, the alloMLR responses 160%, and the production of IL-1 262%. On the contrary, the nonresponders did not show any change in their overall immune status, and in some, deterioration of the already depressed immunologic functions was observed. CONCLUSIONS: Administration of IFN-A2b results in a marked potentiation of deficient cellular immune response in vitro in those patients with RCC who respond to the treatment. This may have prognostic significance, and certainly more patients are required to be studied for definite conclusions.

Adult↗